CYCLIC NUCLEOTIDES AND OTHER SECOND MESSENGERS IN THE NERVOUS SYSTEM

生理功能在不同的细胞中是通过一种 多种第二信使，包括环状AMP和环状GMP。 钙、钠和镁等离子在 通过离子通道或运输蛋白转运，如 第二信使激活离子的释放，并激活 反式蛋白、蛋白激酶、磷脂酶、ATPase和 其他酶。磷脂的酶解也可以 生成第二信使，如花生四烯酸，其作用是 前列腺素的前体；二酰甘油酯，其作用是 蛋白激酶C的激活剂；以及肌醇磷酸盐，它们 作为体内钙离子的激动剂。不同的受体 类型用于调节第二信使的生成。这个 第二信使和受体的相互关系与 用于这种体系的选择性试剂的描述已经被 调查过了。佛波醇酯，它类似于甘油二酯 激活蛋白激酶C，抑制受体介导的 神经母细胞瘤-杂交细胞系中的环磷酸腺苷。各种各样的 激活电压依赖的受体激动剂和药物 钠或钙通道引起磷脂酶C的激活 以及突触神经体中肌醇磷脂的分解。 佛波酯可抑制这些反应。一个很小的亚群 对镉离子高度敏感和低灵敏度的钠离子通道 对河豚毒素的敏感性似乎与 磷酸肌醇代谢。腺苷刺激环磷酸腺苷 通过A2受体形成并抑制环磷酸腺苷 通过A1受体形成。一系列腺苷类似物 已经被取消了药理学特征 参与腺苷生理功能的受体。一个 各种非黄嘌呤杂环，包括一系列N6- 取代-9-甲基腺嘌呤的特征是 腺苷受体拮抗剂某些黄嘌呤类似物已被 显示出作为低血压拮抗剂的选择性作用 腺苷的作用，腺苷的心脏抑制作用 以及腺苷和尼古丁之间的协同作用。

Physiological functions are mediated in different cells by a variety second messengers including cyclic AMP and cyclic GMP. Ions such as calcium, sodium and magnesium can serve after translocation through ion channels or by transport proteins as second messengers to activate release of ions, and activation of contratile proteins, protein kinases, phospholipases, ATPases and other enzymes. Enzymatic hydrolysis of phospholipids can also generate second messengers such as arachidonate, which serves as a precursor of prostanoids; diacylglycerides, which serve as activators of protein kinase C; and inositol phosphates, which serve as mobilizers of internal calcium ions. Receptors of various types serve to modulate generation of second messengers. The interrelationships of second messengers and receptors and the delineation of selective agents for such systems have been investigated. Phorbol esters, which like the diacylglycerides activate protein kinase C, inhibit receptor-mediated formation of cyclic AMP in a neuroblastoma-hybrid cell line. A variety of receptor agonists and agents that activate voltage-dependent sodium or calcium channels cause activation of phospholipase C and breakdown of phosphoinositides in synaptoneurosomes. Phorbol esters inhibit these responses. A small subpopulation of sodium channels with high sensitivity to cadmium ions and low sensitivity to tetrodotoxin appear losely associated with phosphoinositude metabolism. Adenosine stimulates cyclic AMP formation through an A2 receptor and inhibits cyclic AMP formation through an A1 receptor. A series of adenosine analogs have been delinated for pharmacological characterization of receptors involved in physiological functions of adenosine. A variety of non-xanthine heterocycles, including a series of N6- substituted-9-methyladenines have been characterized as adenosine receptor antagonists certain xanthine analogs have been shown to have selective effects as antagonists of the hypotensive effects of adenosine, the cardiac depressant effects of adenosine and the synergism between adenosine and nicotine.