RESUMO
The effects of short-time fasting on appetite, growth, and nutrient were studied in Atlantic salmon (Salmo salar) smolts. Feed deprivation did change the energy metabolism with reduced plasma protein and muscle indispensible amino acid levels. Plasma levels of ghrelin were significantly higher in starved salmon compared with fed fish after 2 days, but no differences in circulating ghrelin were found between treatments after 14 days. Two mRNA sequences for ghrelin-1 and ghrelin-2, 430 and 533 bp long, respectively, were detected. In addition, the growth hormone secretagogues-receptor like receptor (GHSR-LR) 1a and 1b were identified. Ghrelin-1 but not ghrelin-2 mRNA levels were affected by starvation in the stomach. Lower ghrelin-1 mRNA levels were detected at day 2 in starved fish compared with fed fish. The mRNA levels of GHSR-LR1a were not affected by starvation. Fasting reduced the phenotypic growth and the transcription of insulin-like growth factor (IGF)-II together with IGF-IIR, but IGF-I mRNA were not regulated in fasted salmon after 14 days. Three IGF-binding proteins (IGFBP) at 23, 32, and 43 kDa were found in salmon, and circulating 23 kDa was significantly increased after 14 days of starvation compared with fed fish, indicating increased catabolism. The levels of IGFBP-1 mRNA were significantly higher in fed and starved fish after 14 days compared to those at the start of the experiment, but no significant difference was observed between the treatments. In conclusion, we have shown that circulating ghrelin and ghrelin-1 mRNA is related to changes in energy metabolism in Atlantic salmon.
Assuntos
Grelina/metabolismo , Hormônio do Crescimento/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Salmo salar/fisiologia , Inanição/veterinária , Aminoácidos/análise , Aminoácidos/sangue , Animais , Ingestão de Alimentos , Mucosa Gástrica/metabolismo , Regulação da Expressão Gênica , Grelina/sangue , Grelina/química , Grelina/genética , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fígado/metabolismo , Dados de Sequência Molecular , Músculos/química , Músculos/metabolismo , Fenótipo , Filogenia , RNA Mensageiro/metabolismo , Distribuição Aleatória , Salmo salar/classificação , Salmo salar/metabolismo , Somatomedinas/metabolismo , Inanição/fisiopatologia , Fatores de TempoRESUMO
To clarify the role of ghrelin in the fish immune system, the in vitro effect of ghrelin was examined in phagocytic leukocytes of rainbow trout (Oncorhynchus mykiss). Administration of trout ghrelin and des-VRQ-trout ghrelin, in which three amino acids are deleted from trout ghrelin, increased superoxide production in zymosan-stimulated phagocytic leukocytes from the head kidney. Gene expression of growth hormone (GH) secretagogue-receptor (GHS-R) was detected by RT-PCR in leukocytes. Pretreatment of phagocytic leukocytes with a GHS-R antagonist, [D-Lys3]-GHRP-6, abolished the stimulatory effects of trout ghrelin and des-VRQ-trout ghrelin on superoxide production. Ghrelin increased mRNA levels of superoxide dismutase and GH expressed in trout phagocytic leukocytes. Immunoneutralization of GH by addition of anti-salmon GH serum to the medium blocked the stimulatory effect of ghrelin on superoxide production. These results suggest that ghrelin stimulates phagocytosis in fish leukocytes through a GHS-R-dependent pathway, and also that the effect of ghrelin is mediated, at least in part, by GH secreted by leukocytes.
Assuntos
Leucócitos/efeitos dos fármacos , Oncorhynchus mykiss/fisiologia , Hormônios Peptídicos/farmacologia , Fagocitose/efeitos dos fármacos , Superóxidos/metabolismo , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Expressão Gênica/genética , Grelina , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Leucócitos/metabolismo , Oligopeptídeos/farmacologia , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/metabolismo , RNA Mensageiro/análise , Receptores Acoplados a Proteínas G/análise , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores de Grelina , Superóxido Dismutase/análise , Zimosan/farmacologiaRESUMO
Ghrelin injection, either centrally or peripherally strongly stimulates feeding in human and rodents. In contrast, centrally injected ghrelin inhibits food intake in neonatal chickens. No information is available about the mechanism and its relationship with energy homeostasis in chicken. Since ghrelin is predominantly produced in the stomach, we investigated the effect of peripherally injected ghrelin (1 nmol/100g body weight) on food intake and energy expenditure as measured in respiratory cells by indirect calorimetry for 24h in one-week-old chickens. Plasma glucose, triglycerides, free fatty acids, total protein and T(3) were measured in a separate experiment until 60 min after injection. Food intake decreased until at least 1h after intravenous ghrelin administration. The respiratory quotient (RQ) in ghrelin-injected chickens was reduced until 14 h after administration whereas plasma glucose and triglycerides concentrations were not altered. Free fatty acids and total protein levels also remained unchanged. Ghrelin did not influence heat production and this was supported by the absence of changes in plasma T(3) levels when compared to the control values. In conclusion, peripheral ghrelin reduces food intake as well as RQ and might influence the type of substrate (macronutrient) that is used as metabolic fuel.
Assuntos
Galinhas/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Hormônios Peptídicos/farmacologia , Animais , Glicemia/metabolismo , Proteínas Sanguíneas/metabolismo , Calorimetria Indireta/veterinária , Ingestão de Alimentos/fisiologia , Metabolismo Energético/fisiologia , Ácidos Graxos não Esterificados/sangue , Grelina , Injeções Intravenosas , Masculino , Triglicerídeos/sangueRESUMO
The population of synaptic vesicles per synaptic area in the hypothalamic ventromedial nucleus of rats treated with chlorpromazine (CP) for 3 days was compared with that of controls. In type I synapse, which contained 400-800 A small spherical vesicles (s-vesicles), together with 800-1200 A large spherical dense-cored vesicles (lc-vesicles), the population of s-vesicles increased 57.8% in the CP rats, In type II synapse, which contained only s-vesicles, the rate of increase among CP animals was 15.4%. Findings suggested that CP blocks the release of the vesicles from the presynaptic site or inhibits the transport function for biogenic amines through the presynaptic membrane, and type I synapse may be aminergic.
Assuntos
Clorpromazina/farmacologia , Hipotálamo Médio/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Vesículas Sinápticas/ultraestrutura , Animais , Hipotálamo Médio/ultraestrutura , Masculino , Ratos , Vesículas Sinápticas/efeitos dos fármacosRESUMO
Phosphoinositide (PI) turnover was examined by measuring phosphatidic acid (PA) and diacylglycerol (DG) production following thrombin stimulation in platelet membranes from 20 schizophrenic patients, 10 patients with other mental disorders, and 9 normal controls. In 6 of 13 acute schizophrenic patients, DG was not transformed into phosphatidic acid (PA), but accumulated in the platelets instead. The abnormal findings persisted for at least 2 months, but then reversed over a long period. Three years later, the patients with abnormal PI turnover had a significantly better outcome than other acute schizophrenic patients.
Assuntos
Plaquetas/metabolismo , Diglicerídeos/sangue , Glicerídeos/sangue , Fosfatidilinositóis/sangue , Esquizofrenia/sangue , Psicologia do Esquizofrênico , Adolescente , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácidos Fosfatídicos/sangue , Prognóstico , Esquizofrenia/diagnósticoRESUMO
Plasma phospholipid and cholesterol ester fatty acid levels were measured in samples from normal individuals, schizophrenics, and patients with affective and paranoid disorders in Japan. The schizophrenics were divided into groups with normal and reduced platelet sensitivity to the aggregation-inhibiting effects of prostaglandin (PG) E1. As in samples from schizophrenics in several other countries, linoleic acid levels were significantly below normal, as was the ratio of linoleic acid to its metabolites. Phospholipid fatty acid levels were normal in patients with paranoid or affective disorders. When the schizophrenics were divided into those with and without an abnormal response to PGE1, oleic acid was higher and eicosapentaenoic acid lower in those patients with an abnormal response. This study lends further support to the idea that schizophrenics may differ from controls in their essential fatty acid and eicosanoid metabolism.
Assuntos
Ácidos Graxos Essenciais/sangue , Transtornos do Humor/sangue , Fosfolipídeos/sangue , Esquizofrenia/sangue , Adulto , Ésteres do Colesterol/sangue , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
The effects of acute manipulation of plasma osmolality and blood volume on plasma atrial and ventricular natriuretic peptide (ANP and VNP) levels were examined in conscious freshwater eels, Anguilla japonica. A bolus injection of hypertonic NaCl (0.85 M and 1.7 M, 2.5 ml/kg body weight) through a catheter into the ventral aorta produced increases in plasma Na concentration and osmolality with parallel concentration-dependent, transient increases in plasma ANP and VNP levels. Plasma ANP and VNP levels also increased after injection of 1.7 M mannitol solution which produced an increase in plasma osmolality but a decrease in plasma Na concentration. However, injection of a 2.0 M solution of urea, which does not cause cellular dehydration in mammals, produced only small increases in plasma ANP and VNP levels, although plasma osmolality increased. A bolus injection of 10 or 25 ml/kg isotonic saline supplemented with 2% dextran for colloidal osmotic pressure, which theoretically increased blood volume by 29% or 71%, produced volume-dependent, transient increases in plasma ANP and VNP levels without changes in plasma Na concentration and osmolality. Similar volume expansion with dialysed eel plasma caused greater increases than with dextran-saline. However, these increases were much smaller than those after osmotic stimuli. These results indicate that secretion of ANP and VNP is regulated by two receptor mechanisms: osmo-receptors activated by cellular dehydration, not specifically by hypernatraemia, and volume or stretch receptors activated by hypervolaemia. The relative importance of the osmoreceptive mechanism is greater in eels than in mammals where volaemic regulation dominates over osmotic regulation for ANP secretion.
Assuntos
Anguilla/fisiologia , Fator Natriurético Atrial/metabolismo , Volume Sanguíneo/fisiologia , Equilíbrio Hidroeletrolítico/fisiologia , Anguilla/sangue , Animais , Fator Natriurético Atrial/sangue , Concentração Osmolar , Sódio/sangue , Fatores de TempoRESUMO
The individual contributions of, and potential interactions between, the renin-angiotensin system (RAS) and the humoral adrenergic stress response to blood pressure regulation were examined in rainbow trout. Intravenous injection of the smooth muscle relaxant, papaverine (10 mg/kg), elicited a transient decrease in dorsal aortic blood pressure (PDA) and systemic vascular resistance (RS), and significant increases in plasma angiotensin II (Ang II) and catecholamine concentrations. Blockade of alpha-adrenoceptors before papaverine treatment prevented PDA and RS recovery, had no effect on the increase in plasma catecholamines, and resulted in greater plasma Ang II concentrations. Administration of the angiotensin-converting enzyme inhibitor, lisinopril (10(-4) mol/kg), before papaverine treatment attenuated the increases in the plasma concentrations of Ang II, adrenaline, and noradrenaline by 90, 79, and 40%, respectively and also prevented PDA and RS recovery. By itself, lisinopril treatment caused a gradual and sustained decrease in PDA and RS, and reductions in basal plasma Ang II and adrenaline concentrations. Bolus injection of a catecholamine cocktail (4 nmol/kg noradrenaline plus 40 nmol/kg adrenaline) in the lisinopril+papaverine-treated trout, to supplement their circulating catecholamine concentrations and mimic those observed in fish treated only with papaverine, resulted in a temporary recovery in PDA and RS. These results indicate that the RAS and the acute humoral adrenergic response are both recruited during an acute hypotensive stress, and have important roles in the compensatory response to hypotension in rainbow trout. However, whereas the contribution of the RAS to PDA recovery is largely indirect and relies on an Ang II-mediated secretion of catecholamines, the contribution from the adrenergic system is direct and relies at least in part on plasma catecholamines.
Assuntos
Angiotensina II/sangue , Catecolaminas/sangue , Hipotensão/fisiopatologia , Papaverina/farmacologia , Parassimpatolíticos/farmacologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Doença Aguda , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Débito Cardíaco/efeitos dos fármacos , Catecolaminas/farmacologia , Feminino , Hipotensão/sangue , Lisinopril/farmacologia , Masculino , Oncorhynchus mykiss , Radioimunoensaio/métodos , Reprodutibilidade dos Testes , Resistência Vascular/efeitos dos fármacosRESUMO
We purified ghrelin from stomach extracts of a teleost fish, the Japanese eel (Anguilla japonica) and found that it contained an amide structure at the C-terminal end. Two molecular forms of ghrelin with 21 amino acids were identified by cDNA and mass spectrometric analyses: eel ghrelin-21, GSS(O-n-octanoyl)FLSPSQRPQGKDKKPP RV-amide and eel ghrelin-21-C10, GSS(O-n-decanoyl) FLSPSQRPQGKDKKPPRV-amide. Northern blot and RT-PCR analyses revealed high gene expression in the stomach. Low levels of expression were found only in the brain, intestines, kidney and head kidney by RT-PCR analysis. Eel ghrelin-21 increased plasma growth hormone (GH) concentrations in rats after intravenous injection; the potency was similar to that of rat ghrelin. We also examined the effect of eel ghrelin on the secretion of GH and prolactin (PRL) from organ-cultured tilapia pituitary. Eel ghrelin-21 at a dose of 0.1 nM stimulated the release of GH and PRL, indicating that ghrelin acts directly on the pituitary. The present study revealed that ghrelin is present in fish stomach and has the ability to stimulate the secretion of GH from fish pituitary. A novel regulatory pathway of GH secretion by gastric ghrelin seems to be conserved from fish to human.
Assuntos
Enguias/metabolismo , Mucosa Gástrica/metabolismo , Hormônios Peptídicos/análise , Sequência de Aminoácidos , Animais , Bioensaio , Northern Blotting/métodos , Clonagem Molecular , Expressão Gênica , Grelina , Hormônio do Crescimento/metabolismo , Espectrometria de Massas , Dados de Sequência Molecular , Hormônios Peptídicos/genética , Hormônios Peptídicos/farmacologia , Prolactina/metabolismo , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , TilápiaRESUMO
We determined the distribution of orexin-A and orexin-B (also known as hypocretin-1 and hypocretin-2) and their receptors in the rat median eminence and pituitary using sensitive radioimmunoassays coupled with high-performance liquid chromatography, immunohistochemistry, and in situ hybridization. Orexin-A and -B were present in the median eminence, adenohypophysis, and neurohypophysis. Orexin fibers were abundant in the median eminence, and a few fibers projected to the neurohypophysis. Both the orexin(1)- and orexin(2)-receptor mRNAs were expressed robustly in the pituitary intermediate lobe, whereas in the anterior lobe, the orexin(1) receptor was more markedly expressed than the orexin(2) receptor. These two receptor mRNAs were also found in the posterior lobe. These findings may implicate orexin's involvement in additional as yet undefined physiological functions in the hypothalamo-hypophyseal tract.
Assuntos
Proteínas de Transporte/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Eminência Mediana/metabolismo , Neuropeptídeos/metabolismo , Hipófise/metabolismo , Animais , Imuno-Histoquímica , Hibridização In Situ , Masculino , Receptores de Orexina , Orexinas , Coelhos , Radioimunoensaio , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G , Receptores de Neuropeptídeos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Adrenomedullin is a peptide hormone with multifunctional biological properties. Its most characteristic effects are the regulation of circulation and the control of fluid and electrolyte homeostasis through peripheral and central nervous system actions. Although adrenomedullin is a vasodilator of cerebral vasculature, and it may be implicated in the pathomechanism of cerebrovascular diseases, the source of adrenomedullin in the cerebral circulation has not been investigated thus far. We measured the secretion of adrenomedullin by radioimmunoassay and detected adrenomedullin mRNA expression by Northern blot analysis in primary cultures of rat cerebral endothelial cells (RCECs), pericytes and astrocytes. We also investigated the expression of specific adrenomedullin receptor components by reverse transcriptase-polymerase chain reaction and intracellular cAMP concentrations in RCECs and pericytes. RCECs had approximately one magnitude higher adrenomedullin production (135 +/- 13 fmol/10(5) cells per 12 h; mean +/- SD, n = 10) compared to that previously reported for other cell types. RCECs secreted adrenomedullin mostly at their luminal cell membrane. Adrenomedullin production was not increased by thrombin, lipopolysaccharide or cytokines, which are known inducers of adrenomedullin release in peripheral endothelial cells, although it was stimulated by astrocyte-derived factors. Pericytes had moderate, while astrocytes had very low basal adrenomedullin secretion. In vivo experiments showed that adrenomedullin plasma concentration in the jugular vein of rats was approximately 50% higher than that in the carotid artery or in the vena cava. Both RCECs and pericytes, which are potential targets of adrenomedullin in cerebral microcirculation, expressed adrenomedullin receptor components, and exhibited a dose-dependent increase in intracellular cAMP concentrations after exogenous adrenomedullin administration. Antisense oligonucleotide treatment significantly reduced adrenomedullin production by RCECs and tended to decrease intraendothelial cAMP concentrations. These findings may suggest an important autocrine and paracrine role for adrenomedullin in the regulation of cerebral circulation and blood-brain barrier functions. Cerebral endothelial cells are a potential source of adrenomedullin in the central nervous system, where adrenomedullin can also be involved in the regulation of neuroendocrine functions.
Assuntos
Barreira Hematoencefálica/fisiologia , Encéfalo/citologia , Endotélio/citologia , Endotélio/metabolismo , Peptídeos/genética , Adrenomedulina , Animais , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , AMP Cíclico/metabolismo , Expressão Gênica , Oligonucleotídeos Antissenso/farmacologia , Peptídeos/sangue , Pericitos/metabolismo , RNA Mensageiro/análise , Radioimunoensaio , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The inhibitory effects of prostaglandin E1 (PGE1) on the platelet aggregation response (PAR) to adenosine diphosphate (ADP) in 103 schizophrenics, 55 patients with other mental disorders, and 71 controls were examined. The three groups did not differ in PAR to ADP. However, schizophrenic patients, especially in the acute state, showed a significant reduction in the inhibitory effects of PGE1 on PAR compared to the other two groups. These results suggest PGE1 hyposensitivity exists in some schizophrenic patients, which may result from PGE1 deficiency. As clinical characteristics of the subgroup showing platelet PGE1 subsensitivity, relatively successful heterosexual relations, less anergia, and a more severe activation factor on BPRS were identified. Furthermore, the relationship between platelet sensitivity to PGE1 and brain morphology, using magnetic resonance imaging on 39 male schizophrenics was examined. Of 11 parameters obtained from MRI measurements, only callosum: brain ratio showed a significant negative correlation with a platelet sensitivity to PGE1. The current study suggested existence of a subgroup of schizophrenia having platelet hyposensitivity and a definite clinical feature as state markers and small corpus callosum as a trait marker.
Assuntos
Difosfato de Adenosina/antagonistas & inibidores , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Prostaglandinas E/farmacologia , Esquizofrenia/diagnóstico , Difosfato de Adenosina/farmacologia , Adulto , Assistência Ambulatorial , Encéfalo/patologia , Corpo Caloso/patologia , Feminino , Hospitalização , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/diagnóstico , Transtornos Mentais/patologia , Gravidez , Prostaglandinas E/deficiência , Escalas de Graduação Psiquiátrica , Esquizofrenia/sangue , Esquizofrenia/patologia , Psicologia do EsquizofrênicoRESUMO
40 schizophrenic patients and 17 normal controls underwent magnetic resonance imaging (MRI) of the brain. All subjects were consenting males. The size and form of the corpus callosum in the mid-sagittal cut of MRI were evaluated. This study revealed that the mean size of the anterior region of the corpus callosum was significantly greater in schizophrenics than in controls. The elongated anterior corpus callosum, which did not correlate with age, duration of illness, birth complications or any measures of brain areas in the midsagittal cut, was regarded as a primary change. Schizophrenics with the elongated corpus callosum seemed to have an unfavorable prognosis, because the large corpus callosum suggested poor heterosexual relations, reduced number of hospitalizations, low academic grades and mild anxiety-depression syndrome. A smooth and even corpus callosum seen in schizophrenics was likely a change dependent on duration of illness.
Assuntos
Corpo Caloso/patologia , Esquizofrenia/patologia , Adulto , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Adrenomedullin (AM) is an important vasodilator in cerebral circulation, and cerebral endothelial cells are a major source of AM. This in vitro study aimed to determine the AM-induced changes in blood-brain barrier (BBB) functions. AM administration increased, whereas AM antisense oligonucleotide treatment decreased transendothelial electrical resistance. AM incubation decreased BBB permeability for sodium fluorescein (mol. wt 376 Da) but not for Evan's blue albumin (mol. wt 67 kDa), and it also attenuated fluid-phase endocytosis. AM treatment resulted in functional activation of P-glycoprotein efflux pump in vitro. Our results indicate that AM as an autocrine mediator plays an important role in the regulation of BBB properties of the cerebral endothelial cells.
Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Peptídeos/metabolismo , Vasodilatadores/farmacologia , Adrenomedulina , Albuminas/farmacocinética , Animais , Comunicação Autócrina/fisiologia , Barreira Hematoencefálica/fisiologia , Corantes/farmacocinética , Impedância Elétrica , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Azul Evans/farmacocinética , Corantes Fluorescentes/farmacocinética , Técnicas In Vitro , Ratos , Ratos Wistar , Rodamina 123/farmacocinéticaRESUMO
Dopaminergic (DA) synaptic boutons were identified in rat striatum with an electron microscopic histochemical method. In rats which developed behavioral hypersensitivity after treatment with methamphetamine (MAP) for about 2 weeks, significantly fewer DA boutons were found. This effect was specific to DA boutons without mitochondria and was not seen in boutons with mitochondria. The density of granular synaptic vesicles in DA boutons, however, did not change significantly. These morphological changes would represent a high capability of nerve cells to reorganize synaptic connections under altered chemical environments, but they could not be related uniquely to behavioral hypersensitivity, as similar effects were observed in rats treated with haloperidol which did not develop behavioral hypersensitivity. Peculiarly, the effects of MAP treatment on both behavior and DA boutons were prevented by combined administration of haloperidol.
Assuntos
Corpo Estriado/ultraestrutura , Haloperidol/toxicidade , Metanfetamina/toxicidade , Atividade Motora/efeitos dos fármacos , Animais , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Dopamina/metabolismo , Esquema de Medicação , Comportamento Exploratório/efeitos dos fármacos , Haloperidol/administração & dosagem , Masculino , Metanfetamina/administração & dosagem , Microscopia Eletrônica , Ratos , Ratos Endogâmicos , Sono/efeitos dos fármacos , Comportamento Estereotipado/efeitos dos fármacosRESUMO
Based on the results of studies on intracellular signaling in platelets of schizophrenics, an imbalance of the second messenger system is proposed: Diacylglycerol (DG), which activates protein kinase C (PKC), was increased, while adenylate cyclase (AC)-cAMP function was decreased. It is proposed that the increased DG/PKC function may entail a decrease in inositol 1,4,5-trisphosphate (IP3)/Ca2+ function and lowering of phosphoinositide turnover. If such a pathological intracellular signaling takes place in the brain, it may cause a distorted balance of protein activation via phosphorylation in neurons, resulting in some of the deficits of schizophrenia. Neuroleptics have been reported to antagonize the above-mentioned pathological processes of intracellular signaling. The imbalance hypothesis of the DG/PKC pathway and AC-cAMP pathway is not inconsistent with the dopamine hypothesis of schizophrenia, because dopamine receptor stimulation is indirectly related to reduction in IP3/Ca2+ function and lowering of phosphoinositide metabolism.
Assuntos
Diglicerídeos/metabolismo , Modelos Neurológicos , Fosfatidilinositóis/metabolismo , Proteína Quinase C/metabolismo , Esquizofrenia/metabolismo , Sistemas do Segundo Mensageiro , Antipsicóticos/farmacologia , Plaquetas/metabolismo , Cálcio/metabolismo , AMP Cíclico/metabolismo , Humanos , Inositol 1,4,5-Trifosfato/biossíntese , Proteínas do Tecido Nervoso/metabolismo , Fosforilação , Processamento de Proteína Pós-Traducional , Receptores Dopaminérgicos/metabolismo , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Transmissão SinápticaRESUMO
Acetylcholinesterase (AChE) ultracytochemistry with thiocholine method was studied in the rat neostriatum. AChE synthesizing neurons were identified by observing reappearance of the enzyme after application of an AChE inhibitor, DFP. Neurons in the neostriatum were classified into 6 types. All such types were demonstrated to synthesize AChE. Two types of efferent neuron (types III and IV) have shown a relatively large amount of AChE and resynthesized the enzyme in the earlier stage after DFP. A tentative model of the neuronal network in the neostriatum was schematically shown.
Assuntos
Acetilcolinesterase/biossíntese , Corpo Estriado/enzimologia , Neurônios/enzimologia , Animais , Corpo Estriado/ultraestrutura , Masculino , Microscopia Eletrônica , Neurônios/ultraestrutura , RatosRESUMO
In the neostriatum 7.7% of all boutons absorbed alpha-methylnoradrenaline, thus staining their synaptic vesicles profiles granular. These presumably monoaminergic synapses were divided into two types according to ultrastructural features. Type A was composed of a relatively large axon terminal and a dendritic spine with postsynaptic membrane thickening. The axon terminal of type B, that is a bouton en passant, was smaller than the postsynaptic profile, while the synaptic contact was symmetrical. Following nigral coagulation, both types of synapse degenerated. It is concluded that both types of synapse are dopaminergic.
Assuntos
Corpo Estriado/ultraestrutura , Dopamina/fisiologia , Terminações Nervosas/ultraestrutura , Sistema Nervoso Simpático/fisiologia , Animais , Axônios/ultraestrutura , Histocitoquímica , Microscopia Eletrônica , Degeneração Neural , Ratos , Substância Negra/fisiologia , Transmissão SinápticaRESUMO
Immunohistochemical localization of pertussis toxin-sensitive GTP-binding proteins in rat cerebellum was investigated using antibodies raised against purified G alpha o and synthetic peptides corresponding to specific sequences of G alpha i1, G alpha i2 and G alpha o was detected mostly in the molecular layer but not in the cell body of the Purkinje cells. G alpha i1 and G alpha i2 were found predominantly in the molecular layer and in addition in the cell body of the Purkinje cells. G alpha i3 was not detected in rat cerebellum. Immunoblot analysis demonstrated that in the cerebellum membrane G alpha 0 was most abundant and surprisingly the amount of G alpha i2 was much higher than that of G alpha i1. Thus, each pertussis toxin substrate was found to be expressed differently in rat cerebellum. The different patterns of expression imply that each subtype of GTP-binding proteins may have a specific function in modulating the neuronal activity in rat cerebellum.