CYCLIC NUCLEOTIDES AND OTHER SECOND MESSENGERS IN THE NERVOUS SYSTEM

A2-腺苷激动剂诱导的环状AMP蓄积， 脑组织中的β-肾上腺素能、组胺和VIP受体 明显增强的激动剂，提高了周转 磷脂酰肌醇通过与α-肾上腺素能相互作用， H1-组胺和5-羟色胺受体。受体和受体的增强作用 Forskolin介导的环状AMP生成系统的响应出现 可能主要是由于二酰甘油的形成和激活 蛋白激酶C，而不是伴随肌醇的形成 磷酸盐和体内钙的释放：佛波酯直接 蛋白激酶C效应也增强环磷酸腺苷的生成反应 系统，但不会由于以下组合而进一步增强响应 2-氯腺苷和引起磷脂酰肌醇周转的试剂。 腺苷受体显然属于A1亚类，似乎参与了一种 选择性增强组胺诱导的血管内皮细胞蓄积 脑组织中的肌醇磷酸盐。Forsklin的高亲和力结合 TO膜似乎与腺苷环化酶和 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。循环振动的响应 Forskolin和Forsklin的组合在血小板中产生AMP的系统 前列腺素对α2-肾上腺素能激动剂或 P位试剂，2‘，5’-二脱氧腺苷。Forsklin显著增强了 白三烯诱导大鼠皮肤血浆渗出。范围广泛的一些 N6取代的腺苷表现出选择性甚至特异性 脑A1-腺苷受体与冠状动脉A2-受体的比较。这些 腺苷类似物使我们能够详细分析 N6-腺苷受体亚区。强效水溶性腺苷 已经开发出了拮抗剂。这些措施包括 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 表现出明显的选择性，作为A1受体的拮抗剂。一定的 咖啡因类似物，如1，3-二丙基-7-甲基黄嘌呤，表现出一些 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.