RESUMO
The effect of prolonged fasting on sympathetic activity was examined in rat white adipose tissue (WAT) and, for comparison purposes, in interscapular brown adipose tissue (IBAT). Preliminary experiments showed that 6-hydroxydopamine or tyramine administration to fed animals produced similar reductions in norepinephrine (NE) content of WAT and IBAT. Fasting for 48 h did not affect tissue NE content significantly, but induced a threefold increase in [3H]NE uptake by retroperitoneal and epididymal adipose tissue, contrasting with a 50% reduction in IBAT. Measured with DL-alpha-methyl-p-tyrosine, NE fractional rates of turnover were faster and calculated turnover rates were three times higher in retroperitoneal and epididymal tissue from fasted rats than in tissues from fed controls. In experiments with [3H]NE, although fractional rates did not change significantly, calculated NE turnover also increased in retroperitoneal and epididymal tissue after food deprivation. In contrast, in IBAT, NE turnover either did not change (measured with DL-alpha-methyl-p-tyrosine) or, in the experiments with [3H]NE, decreased significantly after fasting. These and other data suggest that a centrally controlled selective activation of WAT sympathetic fibers contributes to fasting lipolysis.
Assuntos
Tecido Adiposo/inervação , Jejum , Sistema Nervoso Simpático/fisiologia , Tecido Adiposo/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Ingestão de Alimentos , Epididimo , Masculino , Metiltirosinas/farmacologia , Norepinefrina/metabolismo , Ratos , Ratos Wistar , Espaço Retroperitoneal , Simpatomiméticos/farmacologia , Fatores de Tempo , Tiramina/farmacologiaRESUMO
We measured the minimum amount of endogenous dopamine (EDA), necessary for the expression of rotational behavior induced by D2 receptor stimulation in striatal or medial forebrain bundle (MFB) lesioned rats. We correlated these results with the minimum dose of D1 receptor agonists needed to substitute EDA in its permissive role for D2 motor effects to take place. Rats with unilateral quinolinic acid (QA) striatal or 6-hydroxydopamine (6-OHDA) MFB lesions were given increasing doses of the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT) in combination with a fixed dose of the D2 receptor agonist quinpirole (trans-(-)-4aR-4,4a,5,6,7,8,8a,9-Octahydro-5-propyl-1H-pyrazolo(3, 4-g) quinoline hydrochloride) and tested for rotational behavior. The animals were later sacrificed and striata removed; EDA was measured by high performance liquid chromatography (HPLC). Rotational responses were abolished by increasing doses of AMPT inducing a stepwise depletion of EDA. EDA content and rotational behavior to D2 stimulation showed a high degree of correlation. There was an abrupt reduction in rotational behavior at dopamine levels of 50-60% of controls in both animal models. In addition, striatal or MFB lesioned rats which were maximally depleted of dopamine by AMPT pretreatment received a fixed dose of quinpirole and then challenged with increasing doses of a D1 receptor agonist SKF 38393 ((+/-)-1-Phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride). Rotational behavior was restored by SKF 38393 in both animal models in a dose-dependent fashion. Our results confirm the need for simultaneous D1/D2 stimulation in the generation of rotational behavior in both animal models. Moreover, they demonstrate the existence of a threshold level of D1 stimulation necessary to exert its permissive role on D2 mediated responses.
Assuntos
Dopamina/análise , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/farmacologia , Animais , Comportamento Animal , Feminino , Metiltirosinas/farmacologia , Quimpirol/farmacologia , Ratos , Ratos Wistar , Rotação , alfa-MetiltirosinaRESUMO
Intracerebroventricular (IVT) administration of renin (R) to conscious male hydrated rats induces an increase in sodium excretion. The involvement of brain dopaminergic neurons in the renal action of IVT-R was investigated. Renin-induced natriuretic action was prevented by domperidone and by inhibition of tyrosine hydroxylase activity with alpha-methyl-p-tyrosine treatment. In addition, this effect was absent following selective central dopaminergic denervation with 6-hydroxydopamine (IVT) in combination with desmethylimipramine (IP). Our results suggest that renin acts centrally, at least in part, via an interaction with endogenous dopamine systems.
Assuntos
Encéfalo/efeitos dos fármacos , Dopamina/fisiologia , Natriurese/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Renina/farmacologia , Animais , Encéfalo/citologia , Domperidona/farmacologia , Antagonistas de Dopamina/farmacologia , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/farmacologia , Injeções Intraventriculares , Masculino , Metiltirosinas/farmacologia , Neurotoxinas , Ratos , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase/antagonistas & inibidores , alfa-MetiltirosinaRESUMO
The difficulty of a reliable diagnosis of pancreatic diseases by scintiscanning, is mainly derived from the lack of adequate radiopharmaceuticals. With this purpose 125I-L-3 Iodo-a-Methyl Tyrosine (125I-IMT) has been studied, which has also been used for the diagnosis of different kind of brain tumors. The purpose of this work is the development of a quick and easy method for the synthesis and purification of the 125I-IMT in order to be used in a Nuclear Medicine Service. The L-alpha-Methyl Tyrosine was labeled with 125I using I-/I03 and afterwards purified by an anionic exchange resin. The labeling yield obtained was (96.0 +/- 0.5)% when the incubation time was 15 minutes. No significant statistical differences were observed when the incubation time was extended to 1 hour. Biodistribution studies in mice show that the percentage of activity concentration in pancreas is (34.24 +/- 14.03)% at 15 minutes post injection, remaining constant for 30 minutes. The pancreas/liver ratio 15 minutes after the injection of the labeled product was (12.22 +/- 3.59) and it remained constant for 45 minutes more. These results show that 125I-IMT can be used as a diagnostic agent for pancreatic diseases. Since 123I was not available at the moment, this new methodology was developed with 125I.
Assuntos
Diagnóstico por Imagem , Metiltirosinas , Neoplasias Pancreáticas/diagnóstico por imagem , Análise de Variância , Animais , Eletroforese em Papel , Radioisótopos do Iodo , Camundongos , CintilografiaRESUMO
The difficulty of a reliable diagnosis of pancreatic diseases by scintiscanning, is mainly derived from the lack of adequate radiopharmaceuticals. With this purpose (125) I-L(-3) Iodo-a-Methyl Tyrosine ((125) I-IMT) has been studied, which has also been used for the diagnosis of different kind of brain tumors. The purpose of this work is the development of a quick and easy method for the synthesis and purification of the (125) I-IMT in order to be used in a Nuclear Medicine Service. The L-(-Methly Tyrosine was labeled with (125) I using I-/I03 and afterwards purified by an aniomic exchange resin. The labeling yield obtained was (96.0+0.5) per cent when the incubation time was 15 minutes. No significant statistical differences were observed when the incubation time was extended to 1 hour. Biodistribution studies in mice show that the percentage of activity concentration in pancreas is (34.24+14.03) per cent at 15 minutes post injection, remaining constant for 30 minutes. The pancreas/liver ratio 15 minutes after the injection of the labeled product was (12.22+3.59) and it remained constant for 45 minutes more. These results show that (125) I-IMT cab be used as a diagnostic agent for pancreatic diseases. Since (123) I was not avilable at the moment, this new methodology was developed with (125) I.
Assuntos
Camundongos , Animais , Diagnóstico por Imagem , Metiltirosinas , Neoplasias Pancreáticas , Análise de Variância , Eletroforese em Papel , Radioisótopos do IodoRESUMO
The difficulty of a reliable diagnosis of pancreatic diseases by scintiscanning, is mainly derived from the lack of adequate radiopharmaceuticals. With this purpose (125) I-L(-3) Iodo-a-Methyl Tyrosine ((125) I-IMT) has been studied, which has also been used for the diagnosis of different kind of brain tumors. The purpose of this work is the development of a quick and easy method for the synthesis and purification of the (125) I-IMT in order to be used in a Nuclear Medicine Service. The L-(-Methly Tyrosine was labeled with (125) I using I-/I03 and afterwards purified by an aniomic exchange resin. The labeling yield obtained was (96.0+0.5) per cent when the incubation time was 15 minutes. No significant statistical differences were observed when the incubation time was extended to 1 hour. Biodistribution studies in mice show that the percentage of activity concentration in pancreas is (34.24+14.03) per cent at 15 minutes post injection, remaining constant for 30 minutes. The pancreas/liver ratio 15 minutes after the injection of the labeled product was (12.22+3.59) and it remained constant for 45 minutes more. These results show that (125) I-IMT cab be used as a diagnostic agent for pancreatic diseases. Since (123) I was not avilable at the moment, this new methodology was developed with (125) I. (AU)
Assuntos
Camundongos , Animais , Neoplasias Pancreáticas/diagnóstico por imagem , Metiltirosinas/diagnóstico , Diagnóstico por Imagem , Radioisótopos do Iodo/diagnóstico , Eletroforese em Papel , Análise de VariânciaRESUMO
The role of para-chlorophenylalanine and alpha-methyl-DL-p-tyrosine in the antinociceptive effects of the intracerebroventricular administration of the antidepressant drugs clomipramine, zimelidine, imipramine and maprotiline was studied using the acetic acid writhing test in mice. The results demonstrated an antinociceptive effect for all these antidepressants. Pretreatment with para-chlorophenylalanine significantly reduced the antinociception induced by the ED50's of imipramine and maprotiline, and did not modify the effects of zimelidine and clomipramine, pretreatment with alpha-methyl-tyrosine did not modify the antinociception induced by these drugs except maprotiline. Pretreatment with para-chlorophenylalanine plus alpha-methyltyrosine significantly reduced the antinociceptive effect of all the antidepressants tested. The main finding of the present study is that the association of para-chlorophenylalanine plus alpha-methyltyrosine reduced the antinociceptive action of all the antidepressants. This means that critical levels of both 5-HT and NA are responsible for mediating the antinociceptive effects of antidepressants on the writhing test in mice.
Assuntos
Analgesia , Antidepressivos/farmacologia , Fenclonina/farmacologia , Metiltirosinas/farmacologia , Serotoninérgicos/farmacologia , Acetatos/administração & dosagem , Acetatos/intoxicação , Ácido Acético , Animais , Clomipramina/farmacologia , Interações Medicamentosas , Fenclonina/administração & dosagem , Imipramina/farmacologia , Injeções Intraventriculares , Maprotilina/administração & dosagem , Maprotilina/farmacologia , Metiltirosinas/administração & dosagem , Camundongos , Norepinefrina/metabolismo , Distribuição Aleatória , Serotonina/metabolismo , Serotoninérgicos/administração & dosagem , Zimeldina/farmacologia , alfa-MetiltirosinaRESUMO
The concentration of dopamine, and its metabolites 3,4-dihydroxyphenylacetic and homovanillic acids, as well as serotonin and its metabolite 5-hydroxyindoleacetic acid, were determined in the retina of two teleosts, C. auratus (goldfish) and E. plumieri (mojarra), and two mammals, R. norvegicus (rat) and O. cuniculus (rabbit). The turnover rate of these monoamines were investigated in the four species by the calculation of the ratio monoamine/metabolite as an indirect index, and in goldfish and rat by the inhibition of the synthesis with alpha-methyl-p-tyrosine or p-chlorophenylalanine, by the increase in dopamine or serotonin by the corresponding precursors, 3,4-dihydroxyphenylalanine or 5-hydroxytryptophan, and by inhibition of monoaminooxidase with pargyline. The modulation by light and dark stimulation was studied in the goldfish and the rat. Differences in the concentration and turnover rate were observed among the species. Serotonin concentration was higher in the teleosts. The administration of inhibitors of dopamine and serotonin synthesis differentially decreased the levels of the monoamines in the retina of goldfish and rat. The rate of formation of dopamine and serotonin by the corresponding precursors was much higher in the goldfish than in the rat. Pargyline administration decreased 3,4-dihydroxyphenylacetic and 5-hydroxyindoleacetic acids at different rates and time dependency in the retina of goldfish and rat. Dopamine and serotonin concentration did not exhibit high modifications by the inhibitor, suggesting the function of regulatory mechanisms or additional effect of pargyline at other sites different from monoaminooxidase.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Dopamina/metabolismo , Carpa Dourada/metabolismo , Luz , Perciformes/metabolismo , Coelhos/metabolismo , Ratos/metabolismo , Retina/metabolismo , Serotonina/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , 5-Hidroxitriptofano/farmacologia , Animais , Carbidopa/farmacologia , Fenclonina/farmacologia , Ácido Homovanílico/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Levodopa/farmacologia , Masculino , Metiltirosinas/farmacologia , Pargilina/farmacologia , Ratos Sprague-Dawley , Retina/efeitos da radiação , Especificidade da Espécie , alfa-MetiltirosinaRESUMO
The release of endogenous DA and DOPAC from nucleus accumbens slices were studied measuring net outflow of DA and DOPAC in the superfusate of static chambers, to analyze the correlation between DA and DOPAC outflows and identify which DA stores may serve as possible sources for DOPAC formation. Under resting conditions, or following stimulation with low (< 15 mM) KCl concentration, DOPAC outflow was greater than DA. When DA release was stimulated by higher (> 25 mM) KCl concentrations, DA outflow increased, proportionally more than DOPAC. In the virtual absence of Ca2+ in the Krebs solution DA outflow, induced by 25 mM KCl, was reduced to about 10%, while DOPAC outflow was only reduced to 45%. When the synthesis of DA was inhibited with alpha-MPT, DA and DOPAC outflow were unchanged during the first stimulation period. During a second stimulation period, however, their outflow were significantly reduced. Nomifensine, a DA uptake inhibitor, increased the basal DA outflow by about 100%, but only blocked DOPAC basal outflow by about 25%. The 25 mM KCl stimulated DA outflow was not affected by Nomifensine, while the stimulated DOPAC outflow was reduced by about 50%. These results demonstrate that there is a weak correlation between the outflows of DA and DOPAC, suggesting a complex relationship between the mobilization of the different DA pools and DOPAC outflow. The formation of DOPAC from some of these pools, appear to be dependent on the stimulation levels and on the pharmacological manipulation of the tissue.
Assuntos
Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Dopamina/metabolismo , Metiltirosinas/farmacologia , Nomifensina/farmacologia , Núcleo Accumbens/metabolismo , Cloreto de Potássio/farmacologia , Sulpirida/farmacologia , Animais , Cálcio/farmacologia , Relação Dose-Resposta a Droga , Ácido Homovanílico/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Técnicas In Vitro , Cinética , Masculino , Núcleo Accumbens/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo , alfa-MetiltirosinaRESUMO
In the rat anococcygeus muscle both dopamine and noradrenaline induced concentration-dependent contractile responses. The alpha 1-antagonist prazosin inhibited both dopamine and noradrenaline responses, whereas the alpha 2-antagonist yohimbine influenced noradrenaline-mediated responses only. The concentration-effect curves for dopamine were shifted to the right in presence of cocaine or after treatment with reserpine and alpha-methyl-p-tyrosine. When the tissues were previously exposed to 6-hydroxydopamine, the tyramine-induced contractile effect was abolished. Dopamine-induced concentration-effect curves were markedly shifted to the right. Treatment with 6-hydroxydopamine and reserpine did not modify the concentration-effect curves to noradrenaline. Our results indicate that dopamine has a dual effect: a partial effect due to an indirect sympathomimetic action and a partial effect due to the interaction with postjunctional receptors.
Assuntos
Dopamina/farmacologia , Músculos/efeitos dos fármacos , Animais , Técnicas In Vitro , Masculino , Metiltirosinas/farmacologia , Contração Muscular/efeitos dos fármacos , Norepinefrina/farmacologia , Oxidopamina/farmacologia , Prazosina/farmacologia , Ratos , Ratos Endogâmicos , Reserpina/farmacologia , Sinapses/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/antagonistas & inibidores , Ioimbina/farmacologia , alfa-MetiltirosinaRESUMO
A possible catecholaminergic regulation of hypothalamic alpha-melanocyte-stimulating hormone (alpha-MSH) has been investigated in male rats by an in vivo approach. The hormone was measured by radioimmunoassay in three hypothalamic regions: medial basal hypothalamus, preoptic hypothalamic area and dorsolateral hypothalamus. The tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (300mg/kg) increased the hypothalamic alpha-MSH content in medial basal hypothalamus and preoptic hypothalamic area when it was measured at 22:00 h. Diethyldithiocarbamate (600mg/kg), which inhibits dopamine beta-hydroxylase, as well as 2-3-dichloromethylbenzylamide (25mg/kg), which acts on the phenylethanolamine-NCH3 transferase also increased the alpha-MSH content in the above mentioned discrete areas. The alpha-adrenoceptor antagonist phenoxybenzamine (15mg/kg), as well as the alpha 1-adrenoceptor antagonist prazosin (1.0mg/kg), also increased the hypothalamic alpha-MSH content in medial basal hypothalamus and preoptic hypothalamic area. None of these agents modified alpha-MSH content in dorsolateral hypothalamus. Haloperidol (1.2mg/kg), a dopaminergic receptor antagonist, propranolol (6.0mg/kg) and yohimbine (10mg/kg) (non selective beta- and alpha 2-adrenergic antagonist drugs respectively) had no effect on the alpha-MSH in any of the hypothalamic areas studied. These results indicate that the catecholaminergic system is involved in the control of proopiomelanocortin derived hypothalamic alpha-MSH through an alpha 1-adrenoreceptor. The data suggest that the control mechanism in the two alpha-MSH hypothalamic pools are different.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Hipotálamo/química , Metiltirosinas/farmacologia , alfa-MSH/análise , Animais , Masculino , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , alfa-MetiltirosinaRESUMO
The circadian rhythm of alpha-amylase, E.C. 3.2.1.1. alpha-1,4-glucan-4-glucanohydrolase) in the parotid glands of 25-day-old rats were studied under different experimental designs (fasting, reversed photoperiod, constant lighting conditions and treatment with reserpine and alpha-methyl-p-tyrosine). The rhythm of fasted rats did not change. There were modifications in the rhythm of rats submitted to a reversed photoperiod or treated with reserpine or alpha-methyl-p-tyrosine. The rhythm was present, with changes in the acrophase, in parotids of rats kept during their gestation and postnatal life in constant light or dark. Results suggest that the circadian rhythm of alpha-amylase in parotid gland of young rats is endogenous, synchronized by the photoperiod, and with maternal coordination.
Assuntos
Envelhecimento/fisiologia , Ritmo Circadiano/fisiologia , Glândula Parótida/enzimologia , alfa-Amilases/fisiologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/efeitos da radiação , Animais , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/efeitos da radiação , Feminino , Privação de Alimentos/fisiologia , Luz , Masculino , Metiltirosinas/farmacologia , Glândula Parótida/efeitos dos fármacos , Glândula Parótida/efeitos da radiação , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Endogâmicos , Reserpina/farmacologia , alfa-Amilases/efeitos dos fármacos , alfa-Amilases/efeitos da radiação , alfa-MetiltirosinaRESUMO
Se investigó una posible regulación catecolaminérgica sobre el alfa-MSH hipotalámico, en ratas machos mediante experimentación "in vivo". La hormona se dosó por radioinmunoensayo en tres regiones hipotalámicas: hipotálamo medial basal (HMB), área preóptica hipotalámica (APO) e hipotálamo dorso-lateral (HDL). Alfa-metil-para-tirosina (300mg/Kg), un inhibidor de la tirosina-hidroxilasa, incrementó el contenido de alfa-MSH en HMB y APO a las 22:00 h. Dietilditiocarbamato (600mg/Kg), que inhibe a la dopamina-b-hidroxilasa, como también 2-3-dicloro-metil-bencil-amida (25mg/Kg), que actua inhibiendo la enzima fenil-etanol-amina transferasa, incrementan el contenido de alfa-MSH en las áreas mencionadas. El antagonista de receptores alfa-adrenérgicos fenoxibenzamina (15mg/Kg) y el antagonista específico de receptores alfa-1, prazosín (1.0mg/Kg) producen el mismo efecto. Ninguna de las drogas experimentadas modificó el contenido de alfa-MSH en el HDL. Haloperidol (1.2mg/Kg), un antagonista de receptores dopaminérgicos, propanolol (6.0mg/Kg) y yohimbina (10mg/Kg) antagonista ß-adrenérgico (no selectivo) y alfa-2 adrenérgico, respectivamente no afectaron el contenido de alfa-MSH en ninguna de las áreas hipotalámicas. Estos resultados indican que el sistema catecolaminérgico estaría involucrado en el control del alfa-MSH hipotalámico derivado de la pro-opiomelanocortina a través de un receptor de tipo alfa-adrenérgico. Los datos sugieren que el mecanismo de control de los dos sistemas hipotámicos productores de alfa-MSH son diferentes
Assuntos
Animais , Masculino , Ratos , Agonistas alfa-Adrenérgicos/farmacologia , alfa-MSH/química , Hipotálamo/química , Metiltirosinas/farmacologia , Radioimunoensaio , Ratos EndogâmicosRESUMO
Se investigó una posible regulación catecolaminérgica sobre el alfa-MSH hipotalámico, en ratas machos mediante experimentación "in vivo". La hormona se dosó por radioinmunoensayo en tres regiones hipotalámicas: hipotálamo medial basal (HMB), área preóptica hipotalámica (APO) e hipotálamo dorso-lateral (HDL). Alfa-metil-para-tirosina (300mg/Kg), un inhibidor de la tirosina-hidroxilasa, incrementó el contenido de alfa-MSH en HMB y APO a las 22:00 h. Dietilditiocarbamato (600mg/Kg), que inhibe a la dopamina-b-hidroxilasa, como también 2-3-dicloro-metil-bencil-amida (25mg/Kg), que actua inhibiendo la enzima fenil-etanol-amina transferasa, incrementan el contenido de alfa-MSH en las áreas mencionadas. El antagonista de receptores alfa-adrenérgicos fenoxibenzamina (15mg/Kg) y el antagonista específico de receptores alfa-1, prazosín (1.0mg/Kg) producen el mismo efecto. Ninguna de las drogas experimentadas modificó el contenido de alfa-MSH en el HDL. Haloperidol (1.2mg/Kg), un antagonista de receptores dopaminérgicos, propanolol (6.0mg/Kg) y yohimbina (10mg/Kg) antagonista ß-adrenérgico (no selectivo) y alfa-2 adrenérgico, respectivamente no afectaron el contenido de alfa-MSH en ninguna de las áreas hipotalámicas. Estos resultados indican que el sistema catecolaminérgico estaría involucrado en el control del alfa-MSH hipotalámico derivado de la pro-opiomelanocortina a través de un receptor de tipo alfa-adrenérgico. Los datos sugieren que el mecanismo de control de los dos sistemas hipotámicos productores de alfa-MSH son diferentes (AU)
Assuntos
Animais , Masculino , Ratos , alfa-MSH/química , Hipotálamo/química , Metiltirosinas/farmacologia , Agonistas alfa-Adrenérgicos/farmacologia , Radioimunoensaio , Ratos EndogâmicosRESUMO
Glutamic acid decarboxylase (GAD) activity was measured in the oviduct of normal rats in diestrous and in rats ovariectomized (OVX) seven days before. OVX induced a significant decrease of GAD activity in the Fallopian tube. This effect was completely reversed by coadministration of estradiol benzoate + progesterone (E + P). Simultaneous injection of atropine, but not of alpha-methyl-para-tyrosine or labetalol, completely prevented the activation of GAD induced by ovarian sterois. Moreover, prostigmin significantly potentiated the action of E + P on GAD activity in the rat oviduct. These data clearly suggest the participation of acetylcholine in the mechanisms whereby ovarian steroids regulate GAD activity in the rat Fallopian tube.
Assuntos
Acetilcolina/fisiologia , Tubas Uterinas/enzimologia , Glutamato Descarboxilase/metabolismo , Ovário/fisiologia , Esteroides/farmacologia , Animais , Atropina/farmacologia , Benzoatos/farmacologia , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Labetalol/farmacologia , Metiltirosinas/farmacologia , Neostigmina/farmacologia , Ovariectomia , Progesterona/farmacologia , Ratos , Ratos Endogâmicos , Receptores Muscarínicos/fisiologia , alfa-MetiltirosinaRESUMO
The mechanism of action of a specific gamma-aminobutyric acid B receptor agonist, beta-p-chlorophenyl-gamma-aminobutyric acid or baclofen, in its inhibitory action on prolactin release, was studied. Dose-response studies of the effect of baclofen on prolactin (PRL) secretion were performed in stressed male rats. Furthermore, the action of the drug was evaluated in (i) rats treated with haloperidol or alpha-methyl-p-tyrosine, (ii) stressed or suckled rats pretreated with sulpiride, and (iii) animals treated with serotonin, alone, or with alpha-methyl-p-tyrosine. Baclofen showed a clear dose-dependent inhibition of prolactin secretion in males under stress. The drug was unable to inhibit the prolactin release induced by haloperidol or alpha-methyl-p-tyrosine, although it reduced the PRL secretion induced by serotonin. It also inhibited PRL release in sulpiride-pretreated stressed or suckled rats. These results suggest that the dose-dependent effect of baclofen on PRL secretion is the consequence of an inhibition exerted on the prolactin-releasing factor component of the neuroendocrine responses evoked by stress or suckling, possibly acting at the serotonergic system.
Assuntos
Baclofeno/farmacologia , Prolactina/metabolismo , Animais , Relação Dose-Resposta a Droga , Feminino , Haloperidol/farmacologia , Masculino , Metiltirosinas/farmacologia , Ratos , Ratos Endogâmicos , Serotonina/farmacologia , Sulpirida/farmacologia , Hormônio Liberador de Tireotropina/metabolismo , alfa-MetiltirosinaRESUMO
The role of dopamine as a neurotransmitter in the retina of different species has been clearly established; however, there is still some controversy as to whether noradrenaline (NA) is present as a neurotransmitter in this tissue. In this study, we show that, under controlled conditions, NA is present in the retina of goldfish at a concentration of 0.15 +/- 0.03 ng/mg protein and its biosynthetic enzyme, dopamine beta-hydroxylase shows an activity of 2.5 +/- 0.2 pmol NA/hr/mg protein. The amount of NA increases to 1.88 +/- 0.24 ng/mg protein in light adapted animals and decreases to undetectable levels in dark adapted ones. By contrast, dopamine-beta-hydroxylase levels are not affected by changes in light conditions. This finding provides further evidence in favor of a neurotransmitter role for NA in vertebrate retina.
Assuntos
Neurotransmissores/fisiologia , Norepinefrina/fisiologia , Retina/fisiologia , Adaptação Fisiológica , Animais , Escuridão , Dopamina/metabolismo , Dopamina beta-Hidroxilase/metabolismo , Ácido Fusárico/farmacologia , Luz , Metiltirosinas/farmacologia , Norepinefrina/metabolismo , Periodicidade , Retina/enzimologia , Retina/metabolismo , Fatores de Tempo , alfa-MetiltirosinaRESUMO
The effect of melatonin injection on norepinephrine (NE) turnover rate in rat pineal gland was estimated from the decline of tissue NE levels after the injection of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine. The administration of a single injection of 300 micrograms/Kg of melatonin at the beginning of the scotophase induced, 3 hr later, a significant decrease of pineal NE turnover. The possible direct effect of melatonin on pineal NE release was examined in vitro. Exposure of rat pineal explants previously loaded with 3H-NE to 10(-8)-10(-6) M melatonin decreased significantly 3H-NE release triggered by 60 mM K+. This activity of melatonin was revealed only in pineals excised at night (0000 and 0400, i.e., at the fourth or eighth hours of darkness) and not in those excised in the middle (1400) or late light phase of the daily photoperiod (2000). Melatonin did not modify the spontaneous pineal 3H-NE efflux. Melatonin decreased 3H-NE uptake at a low NE concentration (0.5 microM) in a dose-dependent manner (IC50 identical to 10(-10) M). A kinetic analysis of the pineal NE uptake process indicated that melatonin augmented both Vmax and Km of transmitter uptake. These results suggest that endogenously released melatonin may be a regulatory signal for rat pineal sympathetic synapses.
Assuntos
Melatonina/farmacologia , Norepinefrina/metabolismo , Glândula Pineal/metabolismo , Análise de Variância , Animais , Ritmo Circadiano/efeitos dos fármacos , Relação Dose-Resposta a Droga , Cinética , Masculino , Metiltirosinas/administração & dosagem , Sistema Nervoso Parassimpático/metabolismo , Glândula Pineal/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Sinapses/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/antagonistas & inibidores , alfa-MetiltirosinaRESUMO
LHRH (100 micrograms/kg. SC) impairs the acquisition of two-way avoidance conditioning. This is partially potentiated by pretreatment with alpha-methyltyrosine (alpha-MT; 250 mg/kg IP) or fusaric acid (10 mg/kg IP). L-DOPA (100 mg/kg IP) administered 5 h after alpha-MT partially reversed its effects. The possible roles of brain catecholamines on the behavioral effects of LHRH are analysed. Other tentative mechanisms of action are also discussed.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Catecolaminas/metabolismo , Hormônio Liberador de Gonadotropina/farmacologia , Animais , Dopamina/metabolismo , Ácido Fusárico/farmacologia , Levodopa/farmacologia , Masculino , Metiltirosinas/farmacologia , Norepinefrina/metabolismo , Ratos , Ratos Endogâmicos , Tirosina 3-Mono-Oxigenase/antagonistas & inibidores , alfa-MetiltirosinaRESUMO
alpha-Methyl-p-tyrosine (alpha-MT), a competitive inhibitor of tyrosine hydroxylase, was used to block the synthesis of hypothalamic catecholamines in immature female rats of 14, 16 and 30 days of age and in castrated adults. The administration of alpha-MT (300 mg/kg body weight, free base) induced a significant decay in the hypothalamic content of norepinephrine (NE) and dopamine (DA) within the first 120 min. A second dose (150 mg/kg body weight), given 2 h after the first injection, did not further modify the low catecholamine levels observed 120 min after the first alpha-MT administration. The administration of 300 mg/kg body weight of alpha-MT induced a significant increase in LH concentrations in rats aged 14 and 16 days. On the contrary, after an alpha-MT injection, a significant LH decrease was observed in 30-day-old and in adult castrated rats. alpha-MT also increased FSH levels in prepubertal rats of 16 days of age, but no change occurred in 30-day-old and in adult rats. The administration of estrogen-progesterone (EP) to prepubertal rats of 16 days of age induced a significant decrease in serum LH levels as well as in the serotonin (5-HT) and 5-hydroxyindole-acetic acid (5-HIAA) concentrations in the anterior-preoptic hypothalamic area (AH-POA), but not in the medial basal hypothalamus. No modifications in the catecholamine content of these hypothalamic areas were observed in this age group after EP administration. On the contrary, in 30-day-old rats, EP induced a significant LH release as well as an increase in AH-POA concentrations of 5-HT, 5-HIAA and catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)