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J Pharmacol Exp Ther ; 305(2): 525-30, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12606693

RESUMO

In mammals, the most important synchronizer for endogenous rhythms is the environmental light/dark cycle. In this report we have explored the ability of light/dark cycle and melatonin, the pineal hormone released during the night, to modulate cerebellar cholinergic input by interfering with the nicotinic acetylcholine receptors' (nAChRs) availability. Through the analysis of the response to selective cholinergic agonists and antagonists, we observed that nAChRs containing the alpha7 gene product mediate the release of [(3)H]glutamate from rat cerebellum slices. The [(3)H]glutamate overflow induced by alpha7 nAChR activation was higher during the dark phase, although the number of alpha-[(125)I]bungarotoxin binding sites, but not the [(3)H]nicotine binding sites (B(max)), was reduced. On the other hand, glutamate-evoked [(3)H]glutamate release was not modified by the hour of the day. Finally, we show that the nocturnal increase in nicotine-evoked [(3)H]glutamate release is imposed by a nocturnal surge of melatonin, as it is abolished when pineal melatonin production is inhibited by either maintaining the animals in constant light for 48 h or by injecting propranolol just before lights off for 2 days. The difference between light and dark [(3)H]glutamate-evoked release is restored in propranolol-treated animals that received melatonin during the dark period. In conclusion, we show that nicotine-evoked [(3)H]glutamate release in rat cerebellum presents a diurnal variation, driven by nocturnal pineal melatonin surge.


Assuntos
Cerebelo/metabolismo , Ácido Glutâmico/metabolismo , Melatonina/fisiologia , Nicotina/farmacologia , Receptores Nicotínicos/fisiologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Cerebelo/efeitos dos fármacos , Colina/farmacologia , Ritmo Circadiano/fisiologia , Escuridão , Técnicas In Vitro , Luz , Masculino , Melatonina/sangue , Nicotina/metabolismo , Agonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Propranolol/farmacologia , Piridinas/farmacologia , Ratos , Ratos Wistar , Receptores Nicotínicos/efeitos dos fármacos , Receptores Nicotínicos/metabolismo , Receptor Nicotínico de Acetilcolina alfa7
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