CYCLIC NUCLEOTIDES AND OTHER SECOND MESSENGERS IN THE NERVOUS SYSTEM

A2-腺苷激动剂引起的环腺苷酸积累， 脑组织中的β-肾上腺素能、H2-组胺和VIP受体是 通过激动剂显著增强， 磷脂酰肌醇通过与肾上腺素-肾上腺素能相互作用， H1-组胺和5-羟色胺受体。 受体的增强作用， 毛喉素介导的环AMP生成系统的反应似乎 这可能主要是由于二酰基甘油的形成和 蛋白激酶C，而不是伴随形成肌醇 磷酸盐和释放内部钙：佛波酯，直接 影响蛋白激酶C也增强环腺苷酸生成反应 系统，但由于以下因素的组合， 2-氯腺苷与引起磷脂酰肌醇周转的药物。 腺苷受体，显然是A1-亚类，似乎参与了一个 选择性增加组胺引起的 脑组织中的肌醇磷酸 毛喉素的高亲和力结合 膜似乎与腺苷酸环化酶的复合物有关， 激活的刺激性鸟嘌呤核苷酸蛋白，并通过 阳离子、氟化物和鸟苷酸。 循环响应 血小板中AMP生成系统与毛喉素和 依那普利对α 2-肾上腺素能激动剂的抑制是难治的， 一种P位点试剂，2 '，5'-双脱氧腺苷。 毛喉素显著增强 白三烯引起大鼠皮肤血浆渗出。 一些广泛的 N6-取代的腺苷表现出选择性或甚至特异性， 脑A1-腺苷受体与冠状动脉A2-受体的比较。 这些 腺苷类似物已经允许详细分析的地形的 腺苷受体N6亚区。 强效水溶性腺苷 已经开发了拮抗剂。 这些包括 1，3-二丙基-8-（对磺基苯基）黄嘌呤。 其他8-苯基黄嘌呤衍生物 作为A1-受体拮抗剂显示出显著的选择性。 某些 咖啡因类似物，例如1，3-二丙基-7-甲基黄嘌呤， 作为A2受体拮抗剂的选择性。

The accumulations of cyclic AMP elicited by agonists for A2-adenosine, beta-adrenergic, H2-histamine and VIP receptors in brain tissue are markedly augmented by agonists that enhance the turnover of phosphatidylinositol through interaction with alphal-adrenergic, H1-histamine and 5HT-serotonin receptors. The potentiation of receptor and forskolin-mediated responses of cyclic AMP-generating systems appears likely due primarily to formation of diacylglycerols and activation of protein kinase C, rather than to the concomitant formation of inositol phosphates and release of internal calcium: Phorbol esters that directly effect protein kinase C also augment responses of cyclic AMP-generating systems, but do not further augment responses due to combinations of 2-chloro-adenosine with agents that cause phosphatidylinositol turnover. Adenosine receptors, apparently of the A1-subclass, appear involved in a selective augmentation of histamine-elicited accumulations of inositolphosphates in brain tissue. The high affinity binding of forskolin to membranes appears associated with a complex of adenylate cyclase and activated stimulatory guanine nucleotide protein and is enhanced by cations, fluoride and guanylnucleotides. The response of cyclic AMP-generating systems in platelets to combinations of forskolin and prostaglandins is refractory to inhibition by alpha2-adrenergic agonists or a P-site agent, 2',5'-dideoxyadenosine. Forskolin markedly potentiates leukotriene-elicited plasma exudation in rat skin. Some of a wide range of N6-substituted adenosines exhibit selectivity or even specificity for a brain A1-adenosine receptor compared to a coronary A2-receptor. These adenosine analogs have allowed a detailed analysis of the topography of the N6-subregion of adenosine receptors. Potent water soluble adenosine antagonists have been developed. These include 1,3-dipropyl-8-(p-sulfophenyl)xanthine. Other 8-phenylxanthine derivatives exhibit marked selectivity as antagonists for A1-receptors. Certain caffeine analogs, such as 1,3-dipropyl-7-methylxanthine, exhibit some selectivity as antagonists for A2-receptors.