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硬骨鱼视网膜中的多巴胺能机制。I. 鲤鱼视网膜匀浆中的多巴胺敏感腺苷酸环化酶;激动剂、拮抗剂和麦角碱的作用。

Dopaminergic mechanisms in the teleost retina. I. Dopamine-sensitive adenylate cyclase in homogenates of carp retina; effects of agonists, antagonists, and ergots.

作者信息

Watling K J, Dowling J E

出版信息

J Neurochem. 1981 Feb;36(2):559-68. doi: 10.1111/j.1471-4159.1981.tb01628.x.

Abstract

A specific dopamine-sensitive adenylate cyclase has been identified in homogenates of the teleost (carp) retina. Maximal stimulation by 100 microM-dopamine resulted in a 5--10-fold increase in adenylate cyclase activity with half-maximal stimulation occurring at a concentration of 1 microM. l-Noradrenaline and l-adrenaline were some 10 times less potent than dopamine whilst the alpha- and beta-adrenoreceptor agonists, l-phenylephrine and dl-isoprenaline were inactive. Apomorphine elicited a partial stimulation of adenylate cyclase activity whilst various ergot alkaloids produced mixed agonist/antagonist responses. Dopamine-stimulated adenylate cyclase activity was potently antagonised by various neuroleptic drugs including fluphenazine, alpha-flupenthixol and alpha-piflutixol, and to a lesser extent by the butyrophenone derivatives haloperidol and spiperone. The benzamide derivatives, metoclopramide and sulpiride, together with the alpha- and beta-adrenoreceptor blocking agents, phentolamine and propranolol respectively were essentially inactive at blocking dopamine-stimulated adenylate cyclase activity. These data suggest the presence of a highly specific dopamine-sensitive adenylate cyclase in homogenates of teleost retina possessing similar pharmacological properties to the dopamine-sensitive adenylate cyclase observed in the mammalian central nervous system.

摘要

在硬骨鱼(鲤鱼)视网膜匀浆中已鉴定出一种特定的多巴胺敏感腺苷酸环化酶。100微摩尔多巴胺的最大刺激导致腺苷酸环化酶活性增加5至10倍,半最大刺激发生在1微摩尔的浓度。左旋去甲肾上腺素和左旋肾上腺素的效力比多巴胺约低10倍,而α和β肾上腺素能受体激动剂,去氧肾上腺素和异丙肾上腺素则无活性。阿扑吗啡引起腺苷酸环化酶活性的部分刺激,而各种麦角生物碱产生混合的激动剂/拮抗剂反应。多巴胺刺激的腺苷酸环化酶活性被包括氟奋乃静、α-氟哌噻吨和α-匹氟噻吨在内的各种抗精神病药物强烈拮抗,而丁酰苯衍生物氟哌啶醇和螺哌隆的拮抗作用较小。苯甲酰胺衍生物甲氧氯普胺和舒必利,以及α和β肾上腺素能受体阻断剂,分别为酚妥拉明和普萘洛尔,在阻断多巴胺刺激的腺苷酸环化酶活性方面基本无活性。这些数据表明,硬骨鱼视网膜匀浆中存在一种高度特异性的多巴胺敏感腺苷酸环化酶,其药理学特性与在哺乳动物中枢神经系统中观察到的多巴胺敏感腺苷酸环化酶相似。

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