RESUMO
Rhodiola rosea L. is one of the most popular adaptogen and an antistress plant in European and Asiatic traditional medicine. Our previous studies have confirmed the adaptogenic and antistress properties of a single administration of R. rosea L. extract in rats exposed to acute stress. There is increasing evidence that prolonged exposure to stressful life events and depression are both related to significant behavioural, endocrinological and neurobiological changes in human and animal subjects. The aim of this study was to determine whether chronic treatment with a hydroalcoholic R. rosea extract (RHO) standardized in 3% rosavin and 1% salidroside can prevent alterations induced in female rats following 6 weeks of a chronic mild stress (CMS) procedure. This was analysed through the behavioural and physiological parameters of consumption of 1% sucrose solution, locomotor and exploratory activities, body weight gain and oestrous cycle length. After the first 3 weeks of stress, RHO was administered daily by gavage at doses of 10, 15 and 20 mg/kg for the remaining 3 weeks. In addition, the antidepressant drug fluoxetine (10 mg/kg os), which has been shown to reverse CMS-induced disruptions, was used as the reference treatment. Rats subjected to the CMS procedure demonstrated decreased sucrose intake, reduced moving behaviour, minimized weight gain and dysregulation of their oestrous cycle. Treatment with RHO completely reverted all of these changes. The effects of RHO were comparable to those of fluoxetine. Interestingly, neither RHO nor fluoxetine influence the behavioural and physiological parameters tested in non-stressed animals. These findings strongly showed that chronic administration of RHO results in potent inhibition of the behavioural and physiological changes induced by chronic exposure to mild stressors.
Assuntos
Antidepressivos/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Rhodiola/química , Estresse Psicológico/tratamento farmacológico , Animais , Antidepressivos/administração & dosagem , Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Doença Crônica , Relação Dose-Resposta a Droga , Ciclo Estral/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Feminino , Atividade Motora/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Raízes de Plantas , Ratos , Ratos Wistar , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Sacarose , Aumento de Peso/efeitos dos fármacosRESUMO
Herein, we provide the first evidence on the capsaicin (CPS) receptor vanilloid receptor type-1 (VR1) by rat thymocytes, and its involvement in CPS-induced apoptosis. VR1 mRNA was identified by quantitative RT-PCR in CD5(+) thymocytes. By immunofluorescence and flow cytometry, we found that a substantial portion of CD5+ thymocytes, namely CD4+ and double negative (DN) cell subsets, express VR1 that was present on plasma membrane on discrete spots. By Western blot, VR1 protein was identified as a single band of 95 kDa. We also described that CPS could trigger two distinct pathways of thymocyte death, namely apoptosis and necrosis depending on the dose of CPS exposure. CPS-induced apoptosis involved intracellular free calcium (Ca2+) influx, phosphatidylserine exposure, mitochondrial permeability transmembrane pore (PTP) opening and mitochondrial transmembrane potential (Delta Psi m) dissipation leading to cytochrome c release, activation of caspase-9 and -3 and oligonucleosomal DNA fragmentation. VR1 was functionally implicated in these events as they were completely abrogated by the VR1 antagonist, capsazepine (CPZ). Finally, we demonstrated that VR1 expression on distinct thymocytes was associated with the selective ability of CPS to trigger DNA fragmentation in VR1+ CD4+ and DN thymocytes. Overall, our results suggest that the expression of VR1 on thymocytes may function as a sensor of harmful stimuli present in the thymic environment.
Assuntos
Apoptose/fisiologia , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Subpopulações de Linfócitos/metabolismo , Receptores de Droga/genética , Linfócitos T/metabolismo , Animais , Apoptose/efeitos dos fármacos , Antígenos CD4/metabolismo , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Antígenos CD5/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Caspases/efeitos dos fármacos , Caspases/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Fragmentação do DNA/efeitos dos fármacos , Fragmentação do DNA/fisiologia , Relação Dose-Resposta a Droga , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/metabolismo , Subpopulações de Linfócitos/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Necrose/induzido quimicamente , Necrose/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de Superfície Celular/efeitos dos fármacos , Receptores de Superfície Celular/metabolismo , Receptores de Droga/biossíntese , Linfócitos T/efeitos dos fármacosRESUMO
The results of the present study show that the intracerebroventricular injection of neurokinin A elicited a selective antidipsogenic effect in the rat. Neurokinin A proved to be an extremely potent inhibitor of drinking elicited by subcutaneous administration of hypertonic NaCl, and produced also a statistically-significant inhibition of food-associated drinking. On the other hand, it did not affect drinking evoked by other dipsogenic determinants, such as water deprivation and intracerebroventricular injection of carbachol or of angiotensin II. Thus, neurokinin A shows a spectrum of antidipsogenic activity clearly different from that of substance P, the other mammalian tachykinin so far tested on drinking behaviour in the rat, which appears to be a non-selective antidipsogenic agent. The findings of the present study suggest that different tachykinins, endogenous to the brain of the rat, might subserve distinct roles in the control of drinking behaviour.
Assuntos
Ingestão de Líquidos/efeitos dos fármacos , Neurocinina A/farmacologia , Angiotensina II/farmacologia , Animais , Carbacol/farmacologia , Privação de Alimentos , Injeções Intraventriculares , Masculino , Neurocinina A/administração & dosagem , Ratos , Ratos Endogâmicos , Cloreto de Sódio/farmacologia , Privação de ÁguaRESUMO
The direct and indirect interaction between the nervous and the immune systems was evaluated in the rat using the neurotoxin capsaicin. Capsaicin treatment of neonatal rats (50 mg/kg at 2 days of age), results in a marked inhibition of mitogen and hrIL-2-induced cell proliferation both in the spleen and peripheral blood. Inhibition is already evident on day 15 after treatment and persists until day 90 in the spleen; at this time a return to control levels is observed in peripheral blood. The inhibition of proliferative response strongly correlates with a decreased number of CD5+ and CD4+ T cells as evaluated by immunofluorescence and FACS analysis. Moreover, continuous in vivo SP administration stimulates mitogen and hrIL-2-induced proliferative response and completely reverts the capsaicin-induced inhibition of lymphocyte proliferation in the spleen.
Assuntos
Capsaicina/farmacologia , Substância P/farmacologia , Linfócitos T/imunologia , Animais , Animais Recém-Nascidos , Capsaicina/imunologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/imunologia , Concanavalina A/farmacologia , Feminino , Interleucina-2/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Mitógenos/farmacologia , Neuropeptídeos/deficiência , Ratos , Ratos Wistar , Organismos Livres de Patógenos Específicos , Baço/citologia , Substância P/imunologia , Linfócitos T/efeitos dos fármacosRESUMO
Substance P (SP) plays a major role in the regulation of the interaction between immune and nervous systems. SP administration stimulates Con A-induced proliferation of spleen and peripheral blood lymphocytes from normal and neonatally capsaicin treated rats, which correlated with enhanced IL-2 production and expression of activation antigens such as IL-2 receptor alpha chain (CD25) and RT1B MHC class II molecule. Moreover, SP markedly increased the percentage of CD5+ and CD4+ T lymphocytes in the peripheral blood of capsaicin-treated rats. Concomitant administration of SP with the non-peptide Neurokinin-1 receptor (NK1R) antagonist SR140333 completely inhibited the SP-mediated augmentation of Con A-induced PBL proliferation and IL-2 production as well as of CD4+ CD25+ and CD4+ RT1B+ T cell numbers in normal and capsaicin-treated rats. SR 140333 also blocked the increased percentage of peripheral blood CD4+ T cells induced by SP in capsaicin-treated rats.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Capsaicina/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Antagonistas dos Receptores de Neurocinina-1 , Substância P/farmacologia , Animais , Linfócitos T CD4-Positivos/química , Linfócitos T CD4-Positivos/citologia , Antígenos CD5/análise , Divisão Celular/efeitos dos fármacos , Divisão Celular/imunologia , Concanavalina A/farmacologia , Feminino , Interleucina-2/biossíntese , Interleucina-2/metabolismo , Masculino , Piperidinas/farmacologia , Quinuclidinas/farmacologia , Ratos , Ratos Wistar , Receptores da Neurocinina-1/imunologia , Organismos Livres de Patógenos Específicos , Baço/citologia , Baço/metabolismoRESUMO
The direct and indirect interaction between the nervous system and its transmitters with the immune system was evaluated in the rat by using the neurotoxin capsaicin (Caps). In the present study we investigated the effect of Caps administration to neonatal rats on thymocyte subpopulation distribution and functions at different times after treatment. Caps treatment results in a marked reduction of thymus weight and cellularity. As shown by immunofluorescence and FACS analysis, profound depletion of double negative (DN), double positive (DP), and single positive (SP) CD4(+) cells was already evident at day 7 after treatment and persisted until day 28. Reduced numbers of SP CD8(+) cells were observed only at later time points. Analysis of TCR phenotype indicates that CD5(+) TCR gamma/delta(+) are particularly sensitive to neonatal Caps treatment. Caps-induced thymocyte depletion was associated with reduced proliferation in response to T cell mitogens. Moreover, in situ TUNEL reaction and agarose gel electrophoresis indicate that neonatal Caps treatment induces apoptosis of thymus cells. Morphological analysis reveals the presence of apoptotic cells in the subcapsular thymus cortical region. Overall our results suggest that Caps when administered at birth, profoundly affects T cell differentiation, likely through its ability to activate apoptotic cell death program.
Assuntos
Timo/citologia , Animais , Animais Recém-Nascidos/fisiologia , Apoptose , Antígenos CD4/análise , Antígenos CD5/análise , Antígenos CD8/análise , Capsaicina/farmacologia , Diferenciação Celular , Divisão Celular/efeitos dos fármacos , Feminino , Masculino , Mitógenos/farmacologia , Ratos , Ratos Wistar , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Timo/efeitos dos fármacos , Timo/imunologia , Timo/fisiologiaRESUMO
The antiproliferative effect of serotonin-reuptake inhibitors (SSRI) and serotonin antagonists has been demonstrated in prostate tumors. Since Hypericum perforatum components act as serotonin-reuptake inhibitors and exert cytotoxic effects on several human cancer cell lines, in this work we analyzed the effect of a treatment with Hypericum perforatum extract (HPE) on the growth of human prostate cancer cells in vitro and in vivo. This study highlighted a significant reduction of tumor growth and number of metastasis suggesting that this natural compound may be useful in the treatment of prostate cancer.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Hypericum/química , Extratos Vegetais/uso terapêutico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/prevenção & controle , Animais , Divisão Celular/efeitos dos fármacos , Humanos , Masculino , Metanol/metabolismo , Camundongos , Camundongos Nus , Neoplasias da Próstata/química , Células Tumorais Cultivadas/transplanteRESUMO
Neurokinin A (NKA), which selectively inhibits only cellular dehydration (CD)-induced drinking in adult rats, exerts a more general antidipsogenic effect in pups in which it also inhibits drinking induced by angiotensin II (AII) or suckling deprivation (SD). The inhibition of drinking is precocious (1st-3rd day) and never involves the intake of milk. The inhibition of CD-induced drinking increases with age, while that of AII- or SD-induced drinking progressively decreases and disappears on day 12-15. In the rat, NKA is therefore a precocious and selective inhibitor of drinking behavior and its selectivity is achieved ontogenetically.
Assuntos
Encéfalo/fisiologia , Ingestão de Líquidos/fisiologia , Neurocinina A/fisiologia , Água/metabolismo , Envelhecimento/fisiologia , Análise de Variância , Angiotensina II/farmacologia , Animais , Animais Lactentes/metabolismo , Feminino , Privação de Alimentos , Injeções Intraventriculares , Masculino , Leite , Neurocinina A/administração & dosagem , Neurocinina A/farmacologia , Ratos , Ratos Endogâmicos , Resposta de Saciedade/efeitos dos fármacos , Resposta de Saciedade/fisiologiaRESUMO
The present study investigated the sensitivity of 12 forebrain and midbrain structures to the antidipsogenic effect of eledoisin, physalaemin and substance P on angiotensin-induced drinking. The three tachykinins elicited the most potent effects when injected into the nucleus preopticus medialis, the nucleus anterior hypothalami and the subfornical organ. In other sites (nuclei lateralis, ventromedialis and posterior hypothalami, nucleus septi lateralis, nucleus interpeduncularis and substantia grisea periventricularis) the effect was lower, and most of these sites showed different sensitivity to the three tachykinins. Finally, the nucleus septi medialis, the nucleus preopticus lateralis and the substantia nigra were refractory to the three tachykinins. These results show that: (1) the antidipsogenic effect of tachykinins can be elicited not only in forebrain, but also in midbrain structures such as the substantia grisea periventricularis and the nucleus interpeduncularis; (2) the distribution of brain sites sensitive to the antidipsogenic effect of substance P and physalaemin is always overlapping, while this is not true for eledoisin. This probably reflects selective distribution and/or activation of distinct subtypes of tachykinin receptors.
Assuntos
Encéfalo/fisiologia , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Neuropeptídeos/farmacologia , Angiotensina II/farmacologia , Animais , Encéfalo/anatomia & histologia , Encéfalo/efeitos dos fármacos , Eledoisina/farmacologia , Masculino , Especificidade de Órgãos , Fisalemina/farmacologia , Ratos , Ratos Endogâmicos , Valores de Referência , Substância P/farmacologia , TaquicininasRESUMO
The effects on ingestive behavior of the naturally occurring bombesin-like peptides ranatensin and litorin were studied in comparison to those of bombesin by intracerebroventricular pulse injection or by continuous infusion in the rat. Ranatensin and litorin, like bombesin, proved to inhibit drinking and feeding behavior. Marked differences, however, were observed in their effects. In particular our results indicate that these peptides possess different selectivity of action on drinking elicited by different dipsogenic stimuli and different potency and effectiveness in inhibiting food intake induced by food deprivation. Moreover, the effects of the three peptides were markedly affected also by the modality of administration (pulse injection or continuous infusion). On the basis of these results it seems possible to hypothesize that the endogenous bombesin-like peptides may differently affect rat ingestive behavior according to their structure and to the rate and modality of their release in the brain.
Assuntos
Bombesina/farmacologia , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Oligopeptídeos/farmacologia , Peptídeos/farmacologia , Vasoconstritores/farmacologia , Animais , Bombesina/administração & dosagem , Privação de Alimentos , Injeções Intraventriculares , Cinética , Masculino , Oligopeptídeos/administração & dosagem , Ácido Pirrolidonocarboxílico/análogos & derivados , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
In infant rats, kassinin exerts its antidipsogenic effect in the very early stages of neonatal life (2nd-3rd day). The inhibition of cell-dehydration drinking appears in rats of 2 days, and attains adult levels in pups of 9 days. Instead, the thirsts induced by suckling deprivation or by intracerebroventricular angiotensin II are inhibited by kassinin precociously (3rd day), but are unaffected by it in rats of 12-15 days. Kassinin also inhibits milk intake very early (3rd day) and this effect also disappears at 12 days of age. The pattern of ontogenetic results described here may be that of a brain kassinin-like tachykinin that, in the course of the development of the neural structures on which it acts, gains potent and selective control of cell-dehydration thirst.
Assuntos
Angiotensina II/farmacologia , Desidratação/fisiopatologia , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Cassinina/farmacologia , Sede/efeitos dos fármacos , Privação de Água , Angiotensina II/administração & dosagem , Animais , Ventrículos Cerebrais/efeitos dos fármacos , Ventrículos Cerebrais/fisiologia , Feminino , Injeções Intraventriculares , Masculino , Leite , Ratos , Saciação/efeitos dos fármacosRESUMO
The present study evaluated the sensitivity of spontaneously hypertensive (SHR) and of Wistar Kyoto (WKY) rats to the hypotensive effect of tachykinins (TKs). Eledoisin, substance P, and the NK-1-selective agonist [Sar9,Met(O2)11]substance P evoked a smaller hypotensive response in SHR than in WKY rats. The hypotensive effect of NKA was slightly smaller in SHR, but no significant strain difference was observed. The NK-2-selective agonist [beta Ala8]NKA(4-10) was a very weak hypotensive agent in WKY rats, while being completely inactive in SHR. The NK-3-selective agonists [Asp5,6,MePhe8]substance P(5-11) and [MePhe7]NKB did not modify blood pressure in both strains. Heart rate was essentially unmodified following the NK-3 agonists, while it was increased after injection of substance P, [Sar9,Met(O2)11]substance P, and neurokinin A, the increase being greater in WKY than in SHR. Surprisingly, eledoisin increased heart rate in SHR, but not in WKY rats, despite the greater hypotensive effect elicited in the latter strain. The present results confirm that the hypotensive effect of peripheral TKs is mediated by NK-1 receptors and show that SHR are less sensitive than WKY rats to this effect.
Assuntos
Hipotensão/induzido quimicamente , Taquicininas/farmacologia , Sequência de Aminoácidos , Animais , Pressão Sanguínea/efeitos dos fármacos , Eledoisina/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Injeções Intravenosas , Masculino , Dados de Sequência Molecular , Neurocinina A/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Substância P/análogos & derivados , Substância P/farmacologia , Taquicininas/administração & dosagem , Taquicininas/químicaRESUMO
This study investigated the sensitivity of spontaneously hypertensive rats (SHR) and of Wistar Kyoto rats (WKR) to the antidipsogenic action of the tachykinin eledoisin (ELE). Drinking was evoked by: (a) intracerebroventricular (i.c.v.) injection of angiotensin II, (b) subcutaneous (s.c.) administration of hypertonic NaCl (1.5 M; 1 ml/100 g b.wt.) or (c) 18 h of water deprivation with free access to food. In accordance with previous studies, the dipsogenic effect of all three treatments was exaggerated in the SHR. And when treated with i.c.v. ELE (12.5-25 ng/rat) they were far less sensitive than WKR to its antidipsogenic action on angiotensin-induced drinking. Smaller differences in strain sensitivity were also observed for the effect of ELE on cell dehydration- and on water deprivation-induced drinking, but only at the dose of 200 and 50 ng/rat, respectively. The different sensitivity of the SHR to the antidipsogenic effect of ELE supports the idea that tachykininergic mechanisms for control of water intake are differently regulated in the SHR than they are in the normotensive WKR.
Assuntos
Angiotensina II/farmacologia , Ingestão de Líquidos/efeitos dos fármacos , Eledoisina/farmacologia , Ratos Endogâmicos SHR , Ratos Endogâmicos , Ratos Endogâmicos WKY , Angiotensina II/administração & dosagem , Animais , Eledoisina/administração & dosagem , Injeções Intraventriculares , Injeções Subcutâneas , Masculino , Ratos , Solução Salina Hipertônica/administração & dosagem , Privação de ÁguaRESUMO
Intracerebroventricular (i.c.v.) injection of kassinin produced a prompt and copious drinking response at doses of 10-1000 ng/pigeon, in the absence of other behavioural alterations or of changes in core temperature. Neurokinin A and B evoked drinking, but they were respectively 10 and 100 times less potent than kassinin. Intraperitoneal injection of kassinin elicited drinking, but at doses about 1000 X larger than the i.c.v. ones. The angiotensin antagonist [Sar1, Leu8]angiotensin II did not reduce drinking induced by i.c.v. kassinin, suggesting that its effect is not due to interaction with the central renin-angiotensin system. Moreover, the effect is apparently independent of the mechanisms controlling hypovolaemic and hyperosmotic thirst since exact additivity was found in the dipsogenic response when i.c.v. kassinin was administered in the presence of a hypovolaemic (subcutaneous (s.c.), polyethylene glycol) or hyperosmotic (s.c. hypertonic NaCl) dipsogenic stimulus. The present findings show that kassinin, neurokinin A and B share with the tachykinins already tested (eledoisin, physalaemin, substance P) a common dipsogenic action in pigeons. However, marked differences exist in their dipsogenic potency. This order of potency, eledoisin = kassinin = physalaemin greater than neurokinin A = substance P greater than neurokinin B, is not consistent with the tachykinin receptor subtypes so far proposed.
Assuntos
Comportamento de Ingestão de Líquido/efeitos dos fármacos , Neuropeptídeos/farmacologia , Oligopeptídeos/farmacologia , Angiotensina II/análogos & derivados , Angiotensina II/farmacologia , Animais , Temperatura Corporal/efeitos dos fármacos , Columbidae , Injeções Intraperitoneais , Injeções Intraventriculares , Cassinina , Masculino , Neurocinina A , Neurocinina BRESUMO
The present study investigated the sensitivity of the medial region of the amygdala to the antinatriorexic action in the rat of the tachykinins eledoisin, substance P, neurokinin A and [Asp5,6, MePhe8] substance P(5-11) (also referred to as amino-senktide; NH2-SENK), which is a highly selective agonist for NK-3 receptors. The results obtained show that only the potent NK-3 agonists eledoisin and NH2-SENK inhibit salt appetite when injected into the medial region of the amygdala. Eledoisin and NH2-SENK inhibited salt appetite induced by sodium depletion, that has been proven to be governed by the synergism of angiotensin and aldosterone. They inhibited also salt appetite evoked by central renin injection, that is due to production of angiotensin II. On the other hand, eledoisin and NH2-SENK did not inhibit salt appetite evoked by subcutaneous deoxycorticosterone treatment. These findings suggest that the medial region of the amygdala is a site of action for the antinatriorexic effect of tachykinins and that their action at this site is mediated by NK-3 receptors. Moreover, our results show that in the medial amygdala, the antinatriorexic action of tachykinins appears to be directed toward the angiotensinergic component of the neural mechanism for salt appetite.
Assuntos
Tonsila do Cerebelo/fisiologia , Apetite/efeitos dos fármacos , Sódio na Dieta , Taquicininas/farmacologia , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Desoxicorticosterona/farmacologia , Eledoisina/farmacologia , Masculino , Neurocinina A/farmacologia , Ratos , Ratos Endogâmicos , Substância P/farmacologiaRESUMO
Pulse intracerebroventricular (i.c.v.) injection of kassinin, 100-500 ng/rat, potently inhibits salt intake induced by sodium depletion. The effect appears to be selective since the same doses of kassinin do not inhibit milk intake or solid food intake. When given by continuous i.c.v. infusion kassinin elicits a clear anti-natriorexic effect at doses of 1-10 ng/min/rat. Kassinin not only suppresses sodium depletion-induced salt appetite, but it also inhibits sodium intake induced by pulse i.c.v. injection of renin or by subcutaneous (s.c.) deoxycorticosterone. Finally it also suppresses the elevated need-free intake of 1.5% NaCl in multidepleted female rats, which is not mediated by the renin-angiotensin-aldosterone system. These findings show that kassinin exerts a general suppressive effect on salt intake, irrespective of the natriorexigenic treatment. The present study suggests that the kassinin-like peptides that are endogenous to the rat brain may be involved in the behavioral regulation of extracellular body fluids in the rat by inhibiting sodium intake.
Assuntos
Apetite/efeitos dos fármacos , Oligopeptídeos/administração & dosagem , Cloreto de Sódio/administração & dosagem , Animais , Desoxicorticosterona/farmacologia , Interações Medicamentosas , Comportamento Alimentar/efeitos dos fármacos , Feminino , Injeções Intraventriculares , Cassinina , Ratos , Ratos Endogâmicos , Renina/farmacologiaRESUMO
The present study investigated the effect of selective muscarinic antagonists on natriuresis, kaliuresis and antidiuresis induced by intracerebroventricular (i.c.v.) injection of carbachol in the rat. The muscarinic antagonists were given by i.c.v. injection 1 min before carbachol (1 microgram/rat). 4-Diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP), a rather selective M1 and M3 receptor antagonist, was the most potent inhibitor of carbachol-induced natriuresis, kaliuresis and antidiuresis, its ID50 being respectively 0.12, 0.04 and 0.56 nmol/rat. Pirenzepine, a selective M1 antagonist, potently inhibited the above mentioned carbachol effects, its ID50 being 1.85, 3.25 and 1.49 nmol/rat, respectively. On the other hand, the M2-selective antagonist methoctramine and the M3-selective antagonist p-fluoro-hexahydro-sila-difenidol were very weak inhibitors. Methoctramine at doses up to 60 nmol/rat produced non statistically significant inhibition of carbachol-induced natriuresis, kaliuresis and antidiuresis. Para-fluoro-hexahydro-sila-diphenidol showed an ID50 of 64.4 nmol/rat on carbachol-induced natriuresis, while at the maximum dose employed, 100 nmol/rat, the inhibition of carbachol-induced kaliuresis and antidiuresis was lower than 50%. The rank order of potency of the antagonists tested proved to be related to their pA2 values for muscarinic M1 receptors, suggesting that this receptor subtype mediates the central effects of cholinergic mechanisms on water and electrolyte excretion.
Assuntos
Carbacol/farmacologia , Diurese/efeitos dos fármacos , Antagonistas Muscarínicos , Natriurese/efeitos dos fármacos , Potássio/urina , Animais , Carbacol/administração & dosagem , Diaminas/farmacologia , Relação Dose-Resposta a Droga , Injeções Intraventriculares , Masculino , Piperidinas/farmacologia , Ratos , Ratos Endogâmicos , Receptores Muscarínicos/fisiologiaRESUMO
We investigated the effect of selective muscarinic antagonists on atrial natriuretic factor (ANF) release induced by intracerebroventricular (i.c.v) injection of carbachol in the rat. The muscarinic antagonists were given by i.c.v. injection 1 min before carbachol, 1 micrograms/rat. 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), a rather selective M1 and M3 receptor antagonist, was the most potent inhibitor of carbachol-induced ANF release, its ID50 being 0.18 nmol/rat. Pirenzepine, a selective M1 antagonist, also potently inhibited the effect of carbachol, its ID50 being 2.74 nmol/rat. The M3-selective antagonist, p-fluoro-hexahydro-sila-diphenidol, was much weaker than pirenzepine, with an ID50 of 57.52 nmol/rat. The selective M2 receptor antagonist, methoctramine, on the other hand, was a very weak inhibitor of carbachol-induced ANF release. The rank order of potency as well as the - log ID50 of the antagonists tested were consistent with their pA2 values for muscarinic M1 receptors, suggesting that this receptor subtype may mediate the central effect of cholinergic mechanisms in the control of ANF release.
Assuntos
Fator Natriurético Atrial/metabolismo , Carbacol/farmacologia , Receptores Muscarínicos/fisiologia , Animais , Fator Natriurético Atrial/sangue , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Carbacol/administração & dosagem , Diaminas/farmacologia , Relação Dose-Resposta a Droga , Injeções Intraventriculares , Injeções Subcutâneas , Masculino , Parassimpatolíticos/farmacologia , Piperidinas/farmacologia , Pirenzepina/farmacologia , Ratos , Ratos Endogâmicos , Receptores Muscarínicos/efeitos dos fármacosRESUMO
The effect of saline and/or water load on diuresis, natriuresis and kaliuresis in control and in neonatal or adult capsaicin-pretreated awake rats has been assessed. Urine was collected by means of metabolic cages or intra-abdominally from a previously catheterized ureter. Neonatal but not adult capsaicin-pretreated animals exhibited a remarkable reduction in volume of urine output and in electrolytes excretion. This effect was more evident following saline as compared to water load. Similar results were also obtained when urine was directly collected from the ureters, suggesting that pharmacological ablation, at neonatal stage, of a subset of capsaicin-sensitive sensory nerves could impair the excretory kidney function.
Assuntos
Capsaicina/farmacologia , Diurese/efeitos dos fármacos , Rim/fisiologia , Envelhecimento , Animais , Feminino , Rim/efeitos dos fármacos , Rim/crescimento & desenvolvimento , Masculino , Natriurese/efeitos dos fármacos , Potássio/urina , Ratos , Ratos Endogâmicos , Valores de ReferênciaRESUMO
The tachykinin peptide [Asp5.6, MePhe8]substance P(5-11) (NH2-senktide), a senktide analogue lacking the N-terminal succinyl group, is a selective and metabolically stable NK-3 receptor agonist. In the present study it potently inhibited salt appetite induced by sodium depletion in rats. Argo-neurokinin B, too, inhibited salt appetite, but was less potent than NH2-senktide. Neither peptide inhibited drinking behaviour induced by subcutaneous hypertonic NaCl. NH2-senktide slightly inhibited angiotensin-induced drinking, while Argo-neurokinin B was ineffective. On the other hand, eledoisin was a potent inhibitor in the 3 behavioural tests. Present results indicate that activation of NK-3 receptors is involved in the antinatriorexic action of tachykinins, and that different receptor subtypes might be involved in the different effects of tachykinins on the rat ingestive behaviour.