CYCLIC NUCLEOTIDES AND OTHER SECOND MESSENGERS IN THE NERVOUS SYSTEM

腺苷通过以下途径调节多种生理功能 与A1和A2腺苷受体的相互作用，其中激动剂可以介导 分别抑制和刺激腺苷环化酶。腺苷 类似物，特别是N6取代化合物，在A1时更有效 而不是A2受体。腺苷受体的亚区 A1和A2与N6-取代基相互作用的方式不同 受体，特别是关于苯基相互作用的受体，整体耐受性 和立体选择性。黄嘌呤是经典的腺苷拮抗剂。 受体及其许多药理作用可能是由于阻断 腺苷受体。咖啡因和茶碱实际上 对A1和A2受体无选择性。取代的甲基 含有正丙基或更大烷基的茶碱可产生黄嘌呤 对A1受体的选择性，特别是与8-苯基结合时 半个月。大多数1，3-二烷基-8-苯基黄嘌呤是非常不溶于水的，但 引入极性芳基取代基，如对磺基或 增加溶解度的对羧基，导致效力显著降低 和选择性。某些咖啡因的类似物，其中甲基位于 1-或7-位被丙叉或丙基取代 A2受体的选择性。一系列腺苷类似物的研究概况 或黄嘌呤拮抗剂可以用来定义腺苷的类别 感受器。受体激动剂和促进钠离子内流的药物 脑突触神经体促进磷脂酰肌醇的周转 在肌醇磷酸盐的积累中。这种受体激动剂和钠 药物同时增加环腺苷酸的蓄积 Forsklin和A2-腺苷受体的作用。佛波醇酯，就像 在磷脂酰肌醇代谢过程中形成的二酰基甘油酯被激活 蛋白激酶，也增加了脑内cAMP的积聚 组织和嗜铬细胞瘤细胞中。

Adenosine modulates a variety of physiological functions through interactions with A1 and A2 adenosine receptors, where agonists can mediate inhibition and stimulation, respectively, of adenylate cyclase. Adenosine analogs, in particular the N6-substituted compounds, are more potent at A1 receptors than at A2 receptors. The subregion of the adenosine receptor that interacts with the N6-substituent is different for A1 and A2 receptors, particularly with respect to phenyl interactions, bulk tolerance and stereoselectivity. Xanthines are classical antagonists for adenosine receptors and many of their pharmacological actions may be due to blockade of adenosine receptors. Caffeine and theophylline are virtually non-selective for A1 and A2 receptors. Replacement of the methyl groups of theophylline with n-propyl or larger alkyl groups yields xanthines with selectivity for A1 receptors, particularly when combined with an 8-phenyl moiety. Most 1,3-dialkyl-8-phenylxanthines are very water insoluble, but incorporation of polar aryl substituents, such as para-sulfo or para-carboxy to increase solubility, results in marked reduction in potency and selectivity. Certain analogs of caffeine in which the methyl group at the 1- or 7-position is replaced with a propargyl or propyl group display selectivity for A2 receptors. The profile of a series of adenosine analogs or of xanthine antagonists can be used to define the class of adenosine receptors. Receptor agonists and agents that enhance influx of sodium into brain synaptoneurosomes enhance turnover of phosphatidylinositols resulting in accumulations of inositol phosphates. Such receptor agonists and sodium agents concomittantly augment accumulations of cyclic AMP elicited by forskolin and by A2-adenosine receptors. Phorbol esters, which like the diacylglycerides formed during phosphatidylinositol metabolism, activate protein kinase, also augment accumulations of cyclic AMP both in brain tissue and in pheochromocytoma cells.