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1.
Neurogastroenterol Motil ; 22(10): 1124-31, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20584261

RESUMEN

BACKGROUND: We have previously demonstrated that a centrally penetrant ghrelin receptor agonist enhances colorectal motility, through activation of the lumbo-sacral defecation center (L6-S1 region of the spinal cord) in rats. In the present study, we examined the effects of the native peptide and its non-acylated counterpart in eliciting this stimulatory effect on colorectal motility. METHODS: Rats were anesthetised with α-chloralose and ketamine, and colorectal intraluminal pressure and propelled intraluminal liquid volume were recorded in vivo. KEY RESULTS: Intrathecal application of acylated ghrelin to the L6-S1 region of the spinal cord, but not intravenous application, elicited groups of phasic increases in colorectal intraluminal pressure that were associated with increased fluid output through the anal cannula. The effect was dose-dependent. The colokinetic effects of ghrelin were prevented if the pelvic nerves were severed. Reverse transcription polymerase chain reaction revealed the expression of the ghrelin and ghrelin receptor genes in the lumbo-sacral spinal cord. In contrast to acylated ghrelin, des-acyl ghrelin failed to cause changes in colorectal motility. However, when des-acyl ghrelin and ghrelin were applied simultaneously at the L6-S1 region, the ghrelin-induced enhancement of colorectal motility was significantly attenuated. CONCLUSION & INFERENCES: It is concluded that acylation of the ghrelin peptide is essential to promote propulsive contractions of the colorectum and that des-acyl ghrelin opposes this effect. At most other sites of ghrelin action, des-acyl ghrelin either has no effect or it mimics ghrelin. This is the first evidence that non-acylated ghrelin opposes the action of the acylated peptide in the spinal cord.


Asunto(s)
Colon/efectos de los fármacos , Defecación/efectos de los fármacos , Defecación/fisiología , Motilidad Gastrointestinal/efectos de los fármacos , Ghrelina/farmacología , Recto/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Médula Espinal/fisiología , Actinas/biosíntesis , Actinas/genética , Acilación , Animales , Relación Dosis-Respuesta a Droga , Ghrelina/biosíntesis , Indicadores y Reactivos , Masculino , Ratas , Ratas Wistar , Receptores de Ghrelina/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
2.
Br J Pharmacol ; 158(3): 888-95, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19694725

RESUMEN

BACKGROUND AND PURPOSE: The chicken anterior mesenteric artery contains an outer longitudinal smooth muscle layer, whose neural regulation remains to be elucidated. ATP evokes a depolarization in the smooth muscle through P2Y purinoceptors. However, there may be an additional inhibitory regulation because blockade of P2Y purinoceptors converts the depolarization to hyperpolarization. The objective of the present study was to examine the mechanism underlying this hyperpolarization. EXPERIMENTAL APPROACH: Membrane potentials of longitudinal smooth muscle of the chicken mesenteric artery were recorded with a microelectrode technique. Perivascular nerves were stimulated by applying electrical field stimulation (EFS). KEY RESULTS: EFS induced a hyperpolarization in preparations obtained from 5-week-old chickens, whereas it evoked a depolarization in those from 12-week-old chickens. The EFS-evoked hyperpolarization in 5-week-old chickens was blocked by a non-specific purinoceptor antagonist, suramin, and by a specific P2X purinoceptor antagonist, pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid. Desensitization of the P2X purinoceptor with its agonist alpha,beta-MeATP significantly suppressed EFS-evoked hyperpolarization. Blockade of the P2Y purinoceptor did not affect EFS-evoked hyperpolarization. The application of the NOS inhibitor Nomega-nitro-L-arginine methyl ester or the removal of the endothelium inhibited the hyperpolarization. The application of the nitric oxide (NO) donor sodium nitroprusside mimicked the hyperpolarization. Reverse transcriptase-PCR showed that P2X purinoceptors are expressed in the endothelium of the anterior mesenteric artery. CONCLUSIONS AND IMPLICATIONS: Hyperpolarization in the longitudinal smooth muscle of the chicken anterior mesenteric artery was induced by ATP. ATP released from perivascular nerves may act on P2X purinoceptors in the endothelium and thereby stimulate NO production.


Asunto(s)
Endotelio Vascular/fisiología , Arterias Mesentéricas/fisiología , Músculo Liso Vascular/fisiología , Receptores Purinérgicos P2/fisiología , Envejecimiento/fisiología , Animales , Pollos , Estimulación Eléctrica , Técnicas In Vitro , Potenciales de la Membrana , Óxido Nítrico/fisiología , Donantes de Óxido Nítrico/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Isoformas de Proteínas/biosíntesis , Agonistas del Receptor Purinérgico P2 , Antagonistas del Receptor Purinérgico P2 , Receptores Purinérgicos P2/biosíntesis
3.
Neurogastroenterol Motil ; 21(2): 180-8, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19077146

RESUMEN

Nitrergic myenteric neurons co-innervating motor endplates were previously shown to inhibit vagally induced contractions of striated muscle in the rodent oesophagus. Immunohistochemical demonstration of putative co-transmitters, e.g. galanin, in enteric neurons prompted us to study a possible role of galanin in modulating vagally mediated contractions in an in vitro vagus nerve-oesophagus preparation of the mouse. Galanin (1-16) (1-100 nmol L(-1)), in the presence of the peptidase inhibitor, phenanthroline monohydrate, inhibited vagally induced contractions in a concentration-dependent manner (control: 100%; galanin 1 nmol L(-1): 95.6 +/- 1.6%; galanin 10 nmol L(-1): 57.3 +/- 6.5%; galanin 100 nmol L(-1): 31.2 +/- 8.1%, n = 5). The non-selective galanin receptor antagonist, galantide (100 nmol L(-1)), blocked the inhibitory effect of galanin (10 nmol L(-1)) while the selective non-galanin receptor 1 and galanin receptor 3 antagonists, M871 (1 micromol L(-1)) and SNAP37889 (100 nmol L(-1)), respectively, and the nitric oxide synthase inhibitor, NG-nitro-l-arginine methyl ester (L-NAME) (200 micromol L(-1)), failed to affect this galanin-induced response. Simultaneous application of galantide (100 nmol L(-1)) and L-NAME (200 micromol L(-1)) significantly reduced the inhibitory effect of capsaicin (30 mumol L(-1)) on vagally induced contractions when compared with its effect in the presence of L-NAME alone or in combination with the selective galanin receptor 2 or 3 antagonists. An inhibitory effect of piperine on vagally induced contractions was reduced neither by galantide nor by L-NAME. Immunohistochemistry revealed galanin immunoreactive myenteric neurons and nerve fibres intermingling with cholinergic vagal terminals at motor endplates. These data suggest that galanin from co-innervating enteric neurons co-operates with nitric oxide in modulating vagally induced contractions in the mouse oesophagus.


Asunto(s)
Esófago/efectos de los fármacos , Esófago/inervación , Galanina/farmacología , Contracción Muscular , Nervio Vago , Alcaloides/farmacología , Animales , Benzodioxoles/farmacología , Capsaicina/farmacología , Estimulación Eléctrica , Inhibidores Enzimáticos/farmacología , Esófago/fisiología , Femenino , Galanina/análogos & derivados , Indoles/farmacología , Masculino , Ratones , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , NG-Nitroarginina Metil Éster/farmacología , Fenantrolinas/metabolismo , Piperidinas/farmacología , Alcamidas Poliinsaturadas/farmacología , Receptores de Galanina/antagonistas & inhibidores , Receptores de Galanina/metabolismo , Fármacos del Sistema Sensorial/farmacología , Sustancia P/análogos & derivados , Sustancia P/farmacología , Nervio Vago/efectos de los fármacos , Nervio Vago/fisiología
4.
Cell Mol Life Sci ; 65(2): 295-311, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17952369

RESUMEN

In the gastrointestinal tract, tachykinins are peptide neurotransmitters in nerve circuits that regulate intestinal motility, secretion, and vascular functions. Tachykinins also contribute to transmission from spinal afferents that innervate the gastrointestinal tract and have roles in the responses of the intestine to inflammation. Tachykinins coexist with acetylcholine, the primary transmitter of excitatory neurons innervating the muscle, and act as a co-neurotransmitter of excitatory neurons. Excitatory transmission is mediated through NK1 receptors (primarily on interstitial cells of Cajal) and NK2 receptors on the muscle. Tachykinins participate in slow excitatory transmission at neuro-neuronal synapses, through NK1 and NK3 receptors, in both ascending and descending pathways affecting motility. Activation of receptors (NK1 and NK2) on the epithelium causes fluid secretion. Tachykinin receptors on immune cells are activated during inflammation of the gut. Finally, tachykinins are released from the central terminals of gastrointestinal afferent neurons in the spinal cord, particularly in nociceptive pathways.


Asunto(s)
Tracto Gastrointestinal/metabolismo , Taquicininas/metabolismo , Animales , Tracto Gastrointestinal/patología , Humanos , Músculo Liso/citología , Músculo Liso/inervación , Péptidos/genética , Receptores de Taquicininas/metabolismo , Transmisión Sináptica , Taquicininas/genética
5.
Res Vet Sci ; 82(2): 246-51, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17034825

RESUMEN

Electrical field stimulation (EFS) induces frequency-dependent contractions of the longitudinal muscle of isolated quail rectum which were sensitive to tetrodotoxin. The aim of the present study was to investigate whether purinergic neurons are implicated in the response to nerve stimulation. The shape of the EFS-induced contractile response was different depending on stimulus frequency; low frequencies (0.5-2 Hz) induced fast monophasic contractions with a small subsequent relaxation; whereas higher frequencies (5-50 Hz) induced biphasic contractile response that comprised fast initial component (as in case of low frequency) and a slow delayed contractile component in addition to the relaxation that follows the fast contractile component. Prior application of atropine (10 microM) completely abolished the slow delayed component but significantly enhanced the fast initial contractile component. Physostigmine (1-10 microM) significantly enhanced the slow delayed component with an inhibitory effect on the initial fast component. The nonspecific purinergic receptor antagonist, suramin (100-500 microM) significantly inhibited the fast initial contractile component with no significant effect on the slow delayed one. Complete blockade of the fast component was achieved by prior application of a combination consisted of suramin (50 microM) and pyridoxicalphosphate-6-azophenyl 2',4'-disulphonic acid tetrasodium (PPADS; 10 microM). Exogenous applications of adenosine 5'-triphosphate and acetylcholine (10 microM each), produced contractile responses that mimicked those induced by EFS. These data suggest that ATP is the main noncholinergic excitatory transmitter controlling the contractile activity of the quail rectum; and that its action could be modulated by acetylcholine.


Asunto(s)
Acetilcolina/fisiología , Adenosina Trifosfato/fisiología , Coturnix/fisiología , Contracción Muscular/fisiología , Receptores Purinérgicos/fisiología , Recto/fisiología , Acetilcolina/farmacología , Animales , Atropina/farmacología , Inhibidores de la Colinesterasa/farmacología , Estimulación Eléctrica , Femenino , Técnicas In Vitro , Masculino , Antagonistas Muscarínicos/farmacología , Contracción Muscular/efectos de los fármacos , Fisostigmina/farmacología , Antagonistas Purinérgicos , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/farmacología , Suramina/farmacología
6.
Pharmacol Res ; 54(6): 452-60, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17035041

RESUMEN

The neurotransmitter(s) that generate the inhibitory junctional potential (IJP) in the circular muscle of hamster distal colon and their mechanisms have not been elucidated. The aim of the present study, therefore, was to determine the contributing roles of the non-adrenergic, non-cholinergic (NANC) inhibitory transmitter(s) including nitric oxide (NO), adenosine 5'-triphosphate (ATP) and vasoactive intestinal polypeptide (VIP) in the generation of IJP in the hamster distal colon. For this purpose, the effects of the corresponding blockers of these putative NANC inhibitory mediators have been investigated using microelectrode technique. Intracellular membrane potential recordings were made from smooth muscle cells at 35 degrees C in Tyrode's solution that contained atropine (0.5microM), guanethidine (3microM) and nifedipine (0.5microM). Single electrical stimuli (0.5ms, 50V) as well as trains of two and five pulses (20Hz at the same duration and voltage) elicited NANC IJP consisted of initial fast (IJP-F) followed by a slow hyperpolarization (IJP-S). The response had been abolished by tetrodotoxin (TTX, 0.3microM). The nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 200microM) blocked IJP-S but enhanced IJP-F. The later had been blocked with suramin, a universal P2 receptor antagonist, or with CBF3GA, a P2Y receptor antagonist at dose-dependent fashions. The IJP-F had been markedly inhibited by desensitization of P2Y receptor with its putative agonist 2-methylthio-ATP (2-meSATP, 50microM for 30min). IJP-F was sensitive to the P2Y1 receptor specific antagonist A3P5PS (10microM) and to the G-protein inhibitor, pertussis toxin (PTX, 400ng/ml for 2h) as well as to the small and intermediate Ca(2+) sensitive K(+) channels blocker, apamin (0.3microM). IJP-S was blocked by the guanylate cyclase (GC) inhibitor, 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10microM) and was partially sensitive to apamin. Exogenously applied ATP (100microM-1mM) produced typical hyperpolarization that was blocked by suramin, CBF3GA and 2-meSATP desensitization; while exogenously applied NO (3-10microM) produced slowly developing hyperpolarization that was not blocked by L-NAME but ODQ. In the presence of both purinergic and nitrergic inhibitors, stimulation using a train of eight pulses at 25Hz evoked a small slow hyperpolarization that was sensitive to the VIP antagonist (VIP 6-28, 1microM). Exogenous application of VIP (1-10microM) produced similar response that was not evident in the presence of VIP 6-28. These data indicate that NANC IJP that is generated in the circular muscle cells of hamster distal colon is mediated by ATP and NO via P2Y1/P2Y2 receptor and GC-dependent pathways, respectively. A masked role for VIP is also indicated.


Asunto(s)
Sistema Nervioso Autónomo/fisiología , Colon/inervación , Unión Neuromuscular/fisiología , Transmisión Sináptica/fisiología , Adenosina Trifosfato/análogos & derivados , Adenosina Trifosfato/farmacología , Animales , Apamina/farmacología , Colon/efectos de los fármacos , Colon/fisiología , Cricetinae , Estimulación Eléctrica , Electrofisiología , Inhibidores Enzimáticos/farmacología , Masculino , Potenciales de la Membrana/fisiología , Mesocricetus , Músculo Liso/fisiología , NG-Nitroarginina Metil Éster/farmacología , Unión Neuroefectora/fisiología , Óxido Nítrico/farmacología , Óxido Nítrico/fisiología , Óxido Nítrico Sintasa de Tipo I/antagonistas & inhibidores , Oxadiazoles/farmacología , Antagonistas Purinérgicos , Quinoxalinas/farmacología , Receptores Purinérgicos/fisiología , Suramina/farmacología , Transmisión Sináptica/efectos de los fármacos , Tionucleótidos/farmacología , Triazinas/farmacología
7.
Neuroscience ; 139(2): 495-503, 2006 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-16458437

RESUMEN

The objective of the present study was to investigate the hypothesis of the presence of a local neural reflex modulating the vagally mediated contractions of striated muscle in the rat esophagus and to determine the possible involvement of tachykinins in such a local neural reflex. Electrical stimulation of the vagus nerve evoked twitch contractile responses that were abolished by d-tubocurarine (5 microM). Capsaicin (1-100 microM) inhibited the vagally mediated twitch contractions o f the normal rat esophageal preparations concentration-dependently but not those of the neonatally capsaicin-treated ones. NG-nitro-L-arginine methyl ester (100 microM), a nitric oxide synthase inhibitor, blocked the inhibitory effect of capsaicin and exogenous application of a nitric oxide donor (1 mM) inhibited the vagally mediated twitch contractions. Capsaicin suppressed acetylcholine release from the normal rat esophageal segments evoked by vagus nerve stimulation but not that from the neonatally capsaicin-treated ones. A selective tachykinin NK1 receptor antagonist (0.1 or 1 microM) attenuated the inhibitory effect of capsaicin. However, antagonists of tachykinin NK2, tachykinin NK3 and calcitonin gene-related peptide receptors (1 microM) did not have any effect. A tachykinin NK1 receptor agonist (1 or 5 microM) inhibited the vagally mediated twitch contractions, which was prevented by NG-nitro-L-arginine methyl ester (100 microM). These data suggest that the rat esophagus might have a local neural reflex inhibiting the vagally mediated striated muscle motility, which consists of capsaicin-sensitive sensory neurons and myenteric nitrergic neurons, and that tachykinins might be involved in the neural reflex through tachykinin NK1 receptors.


Asunto(s)
Esófago/citología , Contracción Muscular/fisiología , Músculo Esquelético/fisiología , Reflejo/fisiología , Taquicininas/fisiología , Acetilcolina/metabolismo , Animales , Animales Recién Nacidos , Atropina/farmacología , Capsaicina/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Inhibidores Enzimáticos/farmacología , Técnicas In Vitro , Masculino , Antagonistas Muscarínicos/farmacología , Contracción Muscular/efectos de la radiación , Músculo Esquelético/efectos de la radiación , NG-Nitroarginina Metil Éster/farmacología , Neurotransmisores/farmacología , Antagonistas Nicotínicos/farmacología , Donantes de Óxido Nítrico/farmacología , Estimulación Física/métodos , Ratas , Ratas Wistar , Taquicininas/antagonistas & inhibidores , Tubocurarina/farmacología
8.
Res Vet Sci ; 79(3): 219-23, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16054891

RESUMEN

The aim of this study was to elucidate the mechanisms underlying the glucose lowering effects of thymoquinone in streptozotocin (STZ)-induced diabetic hamsters in terms of hepatic glucose production. Diabetes was induced by intraperitoneal injection of 65 mg/kg body weight of STZ. Treatment with thymoquinone commenced 4 weeks after induction of diabetes at a daily dose of 50 mg/kg body weight by gastric gauge. Blood glucose and glycated hemoglobin levels were significantly reduced depending on periods of the treatment. Thirty days after commencement of thymoquinone-treatment, hepatocytes were isolated using collagenase to determine liver glucose production. Glucose production after 2 h incubation of the isolated hepatocytes with gluconeogenic precursors (alanine, glycerol and lactate) was significantly lower in hamsters treated with thymoquinone as compared to that in vehicle controls. The results of this study demonstrate that the antidiabetic action of thymoquinone is at least partially mediated through a decrease in hepatic gluconeogenesis.


Asunto(s)
Benzoquinonas/farmacología , Diabetes Mellitus Experimental/metabolismo , Gluconeogénesis/efectos de los fármacos , Glucosa/biosíntesis , Hipoglucemiantes/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Animales , Cricetinae , Diabetes Mellitus Experimental/tratamiento farmacológico , Glucosa/metabolismo , Hemoglobina Glucada/análisis , Hipoglucemiantes/uso terapéutico , Masculino
9.
Acta Diabetol ; 42(1): 23-30, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15868110

RESUMEN

Comparing macrophage-derived cytokine and nitric oxide (NO) profiles in type I and type II diabetes mellitus (DM); and determining whether thymoquinone (TQ) has any modulatory effect were the main objectives of the present study. Peritoneal macrophages have been collected from Otsuka Long-Evans Tokushima Fatty (OLETF) as a model for type II DM and its control Long-Evans Tokushima Otsuka (LETO) rats, as well as from streptozotocin (STZ)-injected LETO ones as a model for type I DM. The cells were cultured and incubated with or without TQ (10 microM) in the absence or presence of lipopolysaccharide (LPS; 1 microg/ml). The same parameters have been also assessed in sera of the used animals with or without TQ treatment (3 mg/kg) under both LPS-stimulated (10 mg/kg) and unstimulated conditions. Nitrite, IL-1beta and TNF-alpha were significantly higher in macrophage supernatants and sera of the acutely affected STZ-LETO rats either with or without LPS stimulation compared to corresponding controls. On the other hand, chronically diabetic OLETF rats' macrophage supernatants showed significant decreases of IL-1beta and TNF-alpha levels upon LPS stimulation or even without stimulation (IL-1beta); and insignificant increase in nitrite concentration, which turned significant upon LPS stimulation. Sera of these animals, however, showed significant increase in TNF-alpha level. TQ normalised the elevated nitrite and cytokine profiles both in vitro and in vivo, yet had no significant effect on the already decreased parameters in chronically affected OLETF rats. These data suggest that there is a tendency for macrophage inflammatory products to increase in acute type I and to decrease in chronic type II DM; and that TQ has the potential to normalise the elevated levels of these macrophage-derived inflammatory mediators.


Asunto(s)
Benzoquinonas/farmacología , Citocinas/metabolismo , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 2/inmunología , Factores Inmunológicos/farmacología , Macrófagos Peritoneales/inmunología , Óxido Nítrico/metabolismo , Animales , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Interleucina-1/sangre , Interleucina-1/metabolismo , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Masculino , Nitritos/sangre , Ratas , Ratas Endogámicas OLETF , Factor de Necrosis Tumoral alfa/metabolismo
10.
Res Vet Sci ; 77(2): 123-9, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15196902

RESUMEN

The aim of this study was to elucidate the mechanisms underlying the hypoglycaemic effect of N. sativa oil (Nigella sativa oil) in streptozotocin (STZ)-induced diabetic hamsters, in terms of hepatic glucose production, and to investigate the possible immunopotentiating effect of N. sativa oil on peritoneal macrophages. Diabetes was induced by intraperitoneal injection of 65 mg/kg body weight of STZ. Treatment with N. sativa oil commenced 6 weeks after induction of diabetes at a dose of 400 mg/kg body weight by gastric gavage. Isolated hepatocytes were collected using collagenase to determine liver glucose production. Phagocytic activity was evaluated by injection of fluorescent latex (2 microm diameter) intraperitoneally, followed 24 h later by collection of peritoneal macrophages. N. sativa oil reduced blood glucose from 391+/-3.0 mg/dl before treatment to 325+/-4.7, 246+/-5.9, 208+/-2.5 and 179+/-3.1 mg/dl after the first, second, third and fourth weeks of treatment, respectively. Hepatic glucose production from gluconeogenic precursors (alanine, glycerol and lactate) was significantly lower in treated hamsters. Treatment with N. sativa oil significantly increased the phagocytic activity and phagocytic index of peritoneal macrophages and lymphocyte count in peripheral blood compared with untreated diabetic hamsters. Our data indicate that the hypoglycaemic effect of N. sativa oil is due to, at least in part, a decrease in hepatic gluconeogenesis, and that the immunopotentiating effect of N. sativa oil is mediated through stimulation of macrophage phagocytic activity either directly or via activation of lymphocytes.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Diabetes Mellitus Experimental/metabolismo , Gluconeogénesis/efectos de los fármacos , Hipoglucemia/metabolismo , Hipoglucemiantes/farmacología , Hígado/efectos de los fármacos , Aceites de Plantas/farmacología , Animales , Glucemia/metabolismo , Cricetinae , Glucosa/metabolismo , Hemoglobina Glucada/metabolismo , Inyecciones Intraperitoneales/veterinaria , Recuento de Leucocitos/veterinaria , Hígado/metabolismo , Activación de Linfocitos/efectos de los fármacos , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/fisiología , Masculino , Mesocricetus , Fagocitosis/fisiología
11.
Life Sci ; 73(15): 1939-51, 2003 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-12899919

RESUMEN

The present study was designed to investigate Substance P (SP) and a related tachykinin, Neurokinin A (NKA), contributions to the excitatory neurotransmission to the circular smooth muscle of the hamster ileum. In the presence of atropine (0.5 microM), guanethidine (3 microM) and NG-nitro-L-arginine methyl ester (L-NAME) (200 microM), electrical field stimulation (EFS) evoked a non-adrenergic, non-cholinergic (NANC) excitatory junction potential (EJP) and contraction of circular smooth muscle. Applications of SP and NKA produced depolarizing and contractile responses in a concentration-dependent fashion. The EJP and contraction were almost abolished by the non-specific tachykininergic antagonist, spantide (3 microM). Application of SP antagonist, L-732,138, (1 microM) markedly inhibited EJP (82.5%) and contraction (68.9%) and completely blocked excitatory responses produced by exogenous application of SP. While application of NKA antagonist, SR48968 (1 microM) completely blocked the depolarising and contractile responses to NKA, it only slightly inhibited those to EFS (17.2% and 31.4% respectively). These results provide evidence that, in the circular muscle of hamster ileum, endogenous tachykinins are the main NANC excitatory neurotransmitters and their action is mediated by both NK1 and NK2 receptors.


Asunto(s)
Íleon/inervación , Neuroquinina A/farmacología , Unión Neuromuscular/fisiología , Receptores de Neuroquinina-1/fisiología , Receptores de Neuroquinina-2/fisiología , Sustancia P/análogos & derivados , Sustancia P/farmacología , Transmisión Sináptica/fisiología , Triptófano/análogos & derivados , Animales , Fármacos del Sistema Nervioso Autónomo/farmacología , Benzamidas/farmacología , Cricetinae , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Íleon/efectos de los fármacos , Íleon/fisiología , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Músculo Liso/efectos de los fármacos , Músculo Liso/inervación , NG-Nitroarginina Metil Éster/farmacología , Antagonistas del Receptor de Neuroquinina-1 , Unión Neuromuscular/efectos de los fármacos , Piperidinas/farmacología , Receptores de Neuroquinina-1/agonistas , Receptores de Neuroquinina-2/agonistas , Receptores de Neuroquinina-2/antagonistas & inhibidores , Transmisión Sináptica/efectos de los fármacos , Triptófano/farmacología
12.
Res Vet Sci ; 73(3): 279-82, 2002 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12443686

RESUMEN

The present study was designed to investigate the possible insulinotropic properties of Nigella sativa L. (N. sativa) oil in Streptozotocin plus Nicotinamide-induced diabetes mellitus in hamsters. Nicotinamide was injected intraperitoneally 15min before injection of Streptozotocin intravenously. Oral treatment with N. sativa oil began 4 weeks after induction of diabetes. Serum insulin was measured by enzymeimmunoassay. Islets insulin was stained using anti-insulin monoclonal antibody. Significant decrease in blood glucose level together with significant increase in serum insulin level were observed after treatment with N. sativa oil for 4 weeks. Big areas with positive immuno-reactivity for the presence of insulin were observed in the pancreases from N. sativa oil-treated group compared to non-treated one using immunohistochemical staining. Therefore, our data show that the hypoglycemic effect of N. sativa oil in Streptozotocin plus Nicotinamide diabetic hamsters resulted, at least partly, from a stimulatory effect on beta cell function with consequent increase in serum insulin level. These results indicate that N. sativa oil has insulinotropic properties in type 2-like model.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insulina/metabolismo , Aceites de Plantas/farmacología , Animales , Glucemia/metabolismo , Cricetinae , Inmunohistoquímica , Insulina/sangre , Masculino , Mesocricetus , Niacinamida/administración & dosificación , Páncreas/metabolismo , Estreptozocina/administración & dosificación
13.
Int Immunopharmacol ; 2(11): 1603-11, 2002 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12433061

RESUMEN

The objective of the present study was to determine the immunomodulatory role of thymoquinone (TQ) regarding its effect on the production of nitric oxide (NO) by rat peritoneal macrophages. Under certain conditions, macrophagesand certain other cells can produce high concentrations of NO from its precursor L-arginine via inducible nitricoxide synthase (iNOS)pathway. TQ has been established as the major component of the oil extracted from Nigella saliva plant seeds, which is being used frequently in herbal medicine. TQ (IC50 1.4-2.76 microM) dose- and time-dependently reduced nitrite production, a parameter for NO synthesis, in supematants of lipopolysaccharide (LPS)-stimulated (5 microg/ml) macrophages without affecting the cell viability. The protein level of iNOS in peritoneal macrophages was also decreased by TQ in a concentration-dependent manner. In addition, TQ inhibited the increase in iNOS mRNA expression induced by LPS indicated by reverse transcription-polymerase chain reaction (RT-PCR). These inhibitory effects of TQ were confirmed by immunofluorescence staining of iNOS in macrophages which showed decreased immunoreactivity for iNOS after treatment with TQ if compared with the control LPS-stimulated cells. These results suggest that TQ suppresses the production of NO by macrophages; an effect which may be useful in ameliorating the inflammatory and autoimmune conditions.


Asunto(s)
Benzoquinonas/farmacología , Macrófagos Peritoneales/enzimología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/biosíntesis , Animales , Western Blotting , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Inmunohistoquímica , Técnicas In Vitro , Indicadores y Reactivos , Macrófagos Peritoneales/efectos de los fármacos , Masculino , Óxido Nítrico Sintasa de Tipo II , ARN Mensajero/biosíntesis , ARN Mensajero/aislamiento & purificación , Ratas , Ratas Endogámicas OLETF , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
14.
Neuroscience ; 110(4): 779-88, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-11934484

RESUMEN

Regulation of vasoactive intestinal peptide (VIP) release by nitric oxide (NO) was investigated in the hamster jejunum. Electrical field stimulation and applied NO (3-100 microM) evoked biphasic hyperpolarizations consisting of an initial transient hyperpolarizing component followed by a second more slowly developing component (late component). The NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (200 microM) abolished the biphasic inhibitory junction potential evoked by electrical field stimulation. The NO scavenger oxyhemoglobin (50 microM) and the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ; 10 microM) abolished both components of the inhibitory junction potentials and the NO-induced hyperpolarizations. VIP(6-28) (1 microM), which abolished VIP (3 microM)-induced hyperpolarizations, also inhibited the late components of the inhibitory junction potentials and the NO-induced hyperpolarizations. ODQ inhibited VIP release and cAMP production by electrical field stimulation and NO application. N(6)-2,0-Dibutyryladenosine 3',5'-cyclic monophosphate (0.1-3 mM) caused a membrane hyperpolarization. These results suggest that NO may stimulate VIP release from enteric nerves in the hamster jejunum. In addition, we propose that NO and NO-stimulated VIP contribute to the early and late components of the inhibitory junction potentials, respectively, in the circular smooth muscle cells of the hamster jejunum.


Asunto(s)
GMP Cíclico/análogos & derivados , Yeyuno/inervación , Músculo Liso/inervación , Plexo Mientérico/metabolismo , Inhibición Neural/fisiología , Neuronas Nitrérgicas/metabolismo , Óxido Nítrico/metabolismo , Transmisión Sináptica/fisiología , Péptido Intestinal Vasoactivo/metabolismo , Animales , Cricetinae , AMP Cíclico/metabolismo , AMP Cíclico/farmacología , GMP Cíclico/farmacología , Estimulación Eléctrica , Inhibidores Enzimáticos/farmacología , Guanilato Ciclasa/antagonistas & inhibidores , Guanilato Ciclasa/metabolismo , Yeyuno/metabolismo , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Mesocricetus , Músculo Liso/metabolismo , Plexo Mientérico/citología , Plexo Mientérico/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Inhibición Neural/efectos de los fármacos , Neuronas Nitrérgicas/citología , Neuronas Nitrérgicas/efectos de los fármacos , Óxido Nítrico/farmacología , Oxadiazoles/farmacología , Oxihemoglobinas/metabolismo , Oxihemoglobinas/farmacología , Fragmentos de Péptidos/farmacología , Inhibidores de Fosfodiesterasa/farmacología , Purinonas/farmacología , Rolipram/farmacología , Transmisión Sináptica/efectos de los fármacos , Péptido Intestinal Vasoactivo/farmacología
15.
J Synchrotron Radiat ; 8(Pt 2): 602-4, 2001 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-11512865

RESUMEN

A characterization of Ti-Beta zeolites synthesized under various conditions as well as an investigation of their photocatalytic properties for the reduction of CO2 with H2O at 323 K to produce CH4 and CH3OH were carried out. In situ XAFS spectra measurements indicated that a highly dispersed tetrahedral titanium oxide species was present in the zeolite framework and an increase in the coordination number of the titanium oxide species by the addition of H2O and CO2 molecules could be detected. The Ti-Beta zeolite having a hydrophilic property (Ti-Beta(OH)) exhibited a more dramatic increase in the coordination number than the Ti-Beta(F) zeolite which had a hydrophobic property. These results suggest that CO2 and H2O molecules can be adsorbed efficiently onto the highly dispersed tetrahedrally coordinated titanium oxide species. UV irradiation of these Ti-Beta zeolite catalysts in the presence of H2O and CO2 led to the formation of CH4 and CH3OH. Ti-Beta(OH) exhibited a higher reactivity than Ti-Beta(F), while the selectivity for the formation of CH3OH on Ti-Beta(F) was higher than that for Ti-Beta(OH). These results indicated that the reactivity and selectivity of the zeolite catalyst can be determined by the hydrophilic and hydrophobic properties of the zeolites.

16.
Neurotoxicology ; 22(2): 191-202, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11405251

RESUMEN

Biochemical events in the initiation of organophosphorus induced delayed neurotoxicity (OPIDN) are not well understood. To find new putative target(s) for OPIDN, we investigated the biochemical and pharmacological characteristics of [3H] diisopropyl phosphorofluoridate (DFP) binding to membrane and cytosol preparations from the brain and spinal cord of hens in vitro. [3H]DFP binding to both preparations was determined by the specific binding obtained by subtracting non-specific binding from total binding. The specific binding sites of [3H]DFP were found not only on membrane but also in cytosol. Kd values were higher and Bmax values were lower in cytosol than in membrane. Moreover, the Kd values in both membrane and cytosol preparations from spinal cord were lower than those of brain. The Bmax values in membrane and cytosol were similar between brain and spinal cord. The specific binding to both preparations was markedly displaced by unlabeled DFP. The specific binding of DFP to the membrane was highly or partly displaced by organophosphorus compounds (OPs) or a carbamate, respectively. However, both the OPs and the carbamate had considerably weaker blocking effects on the specific binding of DFP to cytosol. None of the compounds known to interact with neuropathy target esterase (NTE) had a strong blocking effect on the specific binding of DFP to either membrane or cytosol. These results show that the specific binding of DFP to the membrane may be binding with cholinesterase (ChE). However, cytosol, especially in spinal cord, may have DFP binding sites other than ChE and NTE.


Asunto(s)
Química Encefálica , Pollos/metabolismo , Inhibidores de la Colinesterasa/metabolismo , Citosol/metabolismo , Isoflurofato/metabolismo , Médula Espinal/metabolismo , Animales , Sitios de Unión , Unión Competitiva/efectos de los fármacos , Inhibidores de la Colinesterasa/toxicidad , Inhibidores Enzimáticos/toxicidad , Esterasas/antagonistas & inhibidores , Femenino , Isoflurofato/toxicidad , Membranas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Síndromes de Neurotoxicidad/metabolismo
17.
Neurotoxicology ; 22(2): 203-14, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11405252

RESUMEN

To find new putative target(s) for organophosphorus induced delayed neurotoxicity (OPIDN), we investigated the biochemical and pharmacological characteristics of [3H] diisopropyl phosphorofluoridate (DFP) binding to membrane and cytosol preparations from the brain and spinal cord of hens. Specific [3H]DFP binding was determined by subtracting non-specific binding from total binding. The binding sites of [3H]DFP, an organophosphate that induces OPIDN, were found not only on membrane but also in cytosol. Reduction of subsequent ex vivo specific [3H]DFP binding by in vivo pretreatment with unlabeled DFP was found in cytosol, not membrane. The reduced binding lasted to the onset of OPIDN, especially in spinal cord. These results suggest that the specific DFP binding sites in cytosol, rather than on membrane, are the most important with regard to the initiation of OPIDN. Inhibitors of cholinesterase (ChE) and neuropathy target esterase (NTE) other than DFP did not affect specific [3H]DFP binding to either membranes or cytosol in vivo. Additionally, inhibition of the activities of these esterases by these compounds was not consistent with either the degree of inhibition of the [3H]DFP binding or a time-dependent manner of OPIDN. These results suggest that DFP binding site(s) involved in the initiation of OPIDN may be different from the active sites of ChE and NTE.


Asunto(s)
Hidrolasas de Éster Carboxílico/antagonistas & inhibidores , Pollos/metabolismo , Inhibidores de la Colinesterasa/metabolismo , Inhibidores de la Colinesterasa/toxicidad , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/toxicidad , Isoflurofato/metabolismo , Animales , Sitios de Unión/efectos de los fármacos , Citosol/efectos de los fármacos , Citosol/metabolismo , Femenino , Isoflurofato/toxicidad , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo
18.
J Physiol ; 531(Pt 2): 495-507, 2001 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-11230521

RESUMEN

The present study investigated the effects of hibernation and hibernating body temperature (10 degrees C) on the relative changes that may occur in adrenergic and purinergic perivascular neurotransmission of the golden hamster. The hindlimb resistance vessels and the tibial artery of age-matched controls, cold exposed controls and hibernated hamsters were examined by pharmacological and electrophysiological techniques. At 34 degrees C, electrical field stimulation (EFS; supramaximal voltage, 0.5 ms; for 10 s) in all three groups evoked only twitch responses at 1-5 Hz, which were inhibited by piridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), a 2PX receptor antagonist. At 10-50 Hz the twitch responses were followed by sustained contractile responses, which were inhibited by prazosin, an alpha1-adrenoceptor antagonist. These responses were markedly enhanced at higher frequencies in hibernated tissues. At 10 degrees C, EFS evoked only the PPADS-sensitive transient responses in all the three groups, and this was markedly enhanced in hibernated tissues. At 34 degrees C, a single stimulus evoked a PPADS-sensitive excitatory junction potential (EJP) in all three groups but a train of pulses (e.g. approximately 0.5) evoked EJPs and prazosin-sensitive sustained depolarizations. These responses were markedly enhanced in hibernated cells. At 10 degrees C, either a single stimulus or a train of stimuli evoked only transient PPADS-sensitive EJPs, which were markedly enhanced in hibernated cells. The contractile responses and electrical membrane responses to exogenous ATP (1-1000 microM) and noradrenaline (0.1-100 microM) were unchanged in the three groups at 34 and at 10 degrees C. These results suggest that during hibernation enhancement of ATP release from the sympathetic perivascular nerves may occur, leading to an efficient means for maintenance of vascular tone and peripheral resistance.


Asunto(s)
Adenosina Trifosfato/metabolismo , Hibernación/fisiología , Miembro Posterior/irrigación sanguínea , Miembro Posterior/inervación , Fosfato de Piridoxal/análogos & derivados , Sistema Nervioso Simpático/metabolismo , Adenosina Trifosfato/farmacología , Antagonistas Adrenérgicos alfa/farmacología , Animales , Vasos Sanguíneos/efectos de los fármacos , Vasos Sanguíneos/fisiología , Cricetinae , Estimulación Eléctrica , Electrofisiología , Femenino , Uniones Comunicantes/efectos de los fármacos , Uniones Comunicantes/fisiología , Masculino , Mesocricetus , Norepinefrina/farmacología , Prazosina/farmacología , Fosfato de Piridoxal/farmacología , Temperatura , Vasoconstricción/fisiología
19.
Eur J Pharmacol ; 408(3): 313-21, 2000 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-11090649

RESUMEN

The mechanism of bradykinin-induced hyperpolarisation and purinergic neuromodulation was examined in the hamster superior mesenteric artery using intracellular microelectrode techniques. Bradykinin induced a concentration-dependent hyperpolarisation both in endothelium-intact and -denuded preparations. Indomethacin blocked this hyperpolarisation. Prostacyclin and iloprost also hyperpolarised the membrane of mesenteric artery, while prostaglandin E(2) did not evoke any membrane hyperpolarisation. The bradykinin-, prostacyclin- and iloprost-induced hyperpolarisation were inhibited by glibenclamide. Bradykinin also inhibited the amplitude of the purinergic excitatory junction potentials (e.j.p.s), both in endothelium-intact and -denuded preparations. Indomethacin blocked this inhibitory effect. Prostaglandin E(2) inhibited the e.j. p. in a concentration-dependent manner. Focally applied ATP-induced depolarisation was not modified by bradykinin or prostaglandin E(2.) These findings suggest that bradykinin via prostanoids production pre-synaptically, inhibit the amplitude of purinergic e.j.p., resulting inhibitory purinergic neuromodulation. In addition, bradykinin-released prostanoids elicits membrane hyperpolarisation of smooth muscle cells through opening of K(ATP) channels.


Asunto(s)
Bradiquinina/farmacología , Endotelio Vascular/fisiología , Potenciales de la Membrana/efectos de los fármacos , Arterias Mesentéricas/efectos de los fármacos , Unión Neuromuscular/efectos de los fármacos , Prostaglandinas/biosíntesis , Adenosina Trifosfato/farmacología , Animales , Cricetinae , Dinoprostona/farmacología , Relación Dosis-Respuesta a Droga , Epoprostenol/farmacología , Gliburida/farmacología , Iloprost/farmacología , Indometacina/farmacología , Masculino , Arterias Mesentéricas/citología , Arterias Mesentéricas/fisiología , Mesocricetus , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/fisiología , NG-Nitroarginina Metil Éster/farmacología , Unión Neuromuscular/fisiología , Canales de Potasio/efectos de los fármacos , Prostaglandinas/farmacología
20.
Br J Pharmacol ; 131(5): 942-8, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11053215

RESUMEN

Changes in participation of vasoactive intestinal peptide (VIP) in nonadrenergic noncholinergic (NANC) relaxation of longitudinal muscle of the distal colon with age were studied in 2- to 50-week-old Wistar rats in vitro. The extent of the VIP-mediated component of the relaxation induced by electrical field stimulation (EFS) was determined by the effect of VIP(10 - 28), a VIP receptor antagonist. In 2-week-old rats, the extent of the VIP-mediated component of the relaxation was scarce, about 10%, whereas the component gradually increase with age and reached the maximum extent 66% at 50-week-old. Since our previous results suggest that VIP induces NANC relaxation via activation of charybdotoxin (ChTx, a blocker of large conductance Ca(2+)-activated K(+) channel)-sensitive K(+) channels with concomitant slow hyperpolarization in the muscle cells, we next studied whether ChTx-sensitive component and slow hyperpolarization changes with age. Extent of ChTx-sensitive component of the relaxation increased with age, showing a very similar pattern to VIP-mediated one. EFS induced monophasic inhibitory junction potentials (i.j.ps) in longitudinal muscle cells of the distal colon of 2- and 4-week-old. EFS also induced biphasic i.j.ps in many longitudinal muscle cells of 8- and 50-week-old: rapid and subsequent slow hyperpolarization. A VIP receptor antagonist selectively inhibited the slow hyperpolarization. Exogenously added VIP induced no appreciable change in the membrane potential of longitudinal muscle cells of 2-week-old, whereas it induced slight slow hyperpolarization of the cell membrane in 4-week-old and magnitude of the hyperpolarization increased with age. On the other hand, relaxant response of the longitudinal muscle to exogenously added VIP was high in younger rats. The present results suggest that the role of VIP in mediating NANC relaxation of longitudinal muscle of the Wistar rat distal colon is very little at neonatal stage, but it increases with age.


Asunto(s)
Colon/efectos de los fármacos , Péptido Intestinal Vasoactivo/fisiología , Factores de Edad , Animales , Caribdotoxina/farmacología , Colon/inervación , Colon/fisiología , Estimulación Eléctrica , Femenino , Masculino , Potenciales de la Membrana/efectos de los fármacos , Óxido Nítrico/fisiología , Ratas , Ratas Wistar , Péptido Intestinal Vasoactivo/análisis
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