REGULATION OF CYCLIC NUCLEOTIDE MECHANISMS

1)cAMP和cGMP是关键的细胞内信使，在细胞内的调控下， 外源性因子。 在NIE-115细胞中，毒蕈碱激动剂影响NIE-115细胞和NIE-115细胞。 cAMP和cGMP，分别引起抑制和升高。 毒蕈碱 cAMP磷酸二酯酶不能阻断cAMP水平的抑制 抑制剂，因此是由腺苷酸环化酶的抑制引起的， 磷酸二酯酶的活化。 毒蕈碱类药物的抑制作用 对cAMP的作用是由鸟苷酸结合蛋白Gi介导的; 它们影响cGMP生成的机制尚不清楚。 百日咳 毒素通过催化Gi的ADP-核糖基化， 抑制基础和胰高血糖素刺激的cAMP。 毒素没有 影响毒蕈碱激动剂依赖性cGMP水平，与 假设Gi不参与该途径。 2)NAD：精氨酸 以前在动物组织中鉴定的ADP-核糖基转移酶催化 类似于细菌毒素的反应，如霍乱原， 腺苷酸环化酶的激活。 催化反应动力学 检查了胆固醇原和红细胞ADP-核糖基转移酶， 胍丁胺，精氨酸类似物，作为ADP-核糖受体。 对数据进行 最符合随机、快速平衡、顺序机制; NAD或胍基丁胺的结合对随后的 另一种基质的结合。 3)NAD：精氨酸ADP-核糖基转移酶 催化精氨酸和蛋白质的ADP-核糖基化。 酶 在红细胞中鉴定了切割ADP-核糖基精氨酸以 ADP-核糖和精氨酸。 反应受二价阳离子的刺激 (e.g., Mg 2+）和硫醇。 反应的产物精氨酸，在 存在NAD、ADP-核糖基化的促胆固醇原和红细胞 转移酶 由于ADP-核糖基精氨酸的去极化产生精氨酸， 作为转移酶底物的部分，似乎 ADP-核糖基化可以是可逆的共价修饰。

1) cAMP and cGMP, are critical intracellular messengers, under the control of exogenous agents. In NlE-ll5 cells, muscarinic agonists affect both cAMP and cGMP, causing suppression and elevation, respectively. Muscarinic suppression of cAMP levels was not blocked by cAMP phosphodiesterase inhibitors, and thus results from inhibition of adenylate cyclase and not activation of phosphodiesterase. Inhibitory effects of muscarinic agents on cAMP are mediated by a guanyl nucleotide-binding protein, Gi; the mechanism by which they influence cGMP generation is unclear. Pertussis toxin, by catalyzing the ADP-ribosylation of Gi, reduced the muscarinic suppression of basal and prostaglandin-stimulated cAMP. The toxin did not affect muscarinic agonist-dependent cGMP levels, consistent with the hypothesis that Gi is not involved in this pathway. 2) NAD:arginine ADP-ribosyltransferases, previously identified in animal tissues, catalyze reactions similar to bacterial toxins, such as choleragen, which cause activation of adenylate cyclase. Kinetics of the reactions catalyzed by choleragen and an erythrocyte ADP-ribosyltransferase were examined with agmatine, an arginine analogue, as the ADP-ribose acceptor. The data were most consistent with a random, rapid equilibrium, sequential mechanism; binding of either NAD or agmatine had a negative effect on the subsequent binding of the other substrate. 3) NAD:arginine ADP-ribosyltransferases catalyze the ADP-ribosylation of arginine and proteins. An enzymatic activity was identified in erythrocytes that cleaved ADP-ribosylarginine to ADP-ribose and arginine. The reaction was stimulated by divalent cations (e.g., Mg2+) and thiols. A product of the reaction, arginine, was, in the presence of NAD, ADP-ribosylated by choleragen and erythrocyte transferase. Since deradation of ADP-ribosylarginine generates an arginine moiety that is a substrate for the transferases, it appears that ADP-ribosylation may be a reversible covalent modification.