Mittag T W, Tormay A, Podos S M
Department of Ophthalmology, Mount Sinai School of Medicine, CUNY 10029.
Exp Eye Res. 1988 Jun;46(6):841-51. doi: 10.1016/s0014-4835(88)80036-8.
Manganous chloride was compared with magnesium chloride in supporting maximal stimulations of the adenylate cyclase system in ocular ciliary process membranes by isoproterenol, vasoactive intestinal peptide, sodium fluoride, guanosine 5'-(beta, gamma-imino) triphosphate (GppNHp), or forskolin, and in supporting synergism between isoproterenol and forskolin. The primary effect of Mn2+ (2 mM) was due to an interaction at the catalytic unit. Mn2+ had no significant effect on the function of the GTP-binding stimulatory G-protein (Gs) which couples beta-adrenergic receptors to the catalytic unit of adenylate cyclase. However, Gs-protein function was impaired by Mn2+ relative to Mg2+ when GppNHp was used instead of GTP as the ligand for the Gs-protein. Compared with Mg2+, Mn2+ caused a 4-5.5-fold increase in adenylate cyclase responsiveness to all the activators tested (except GppNHp, where the increase was 2.5-3.5-fold). Thus Mn2+ ions appeared to be intrinsically more effective at divalent cation binding sites on the catalytic unit that control its enzymatic activity. Ciliary process membranes differ from erythrocyte and S49 lymphoma cell membranes where 2 mM Mn2+ strongly inhibits hormone-Gs-protein-mediated stimulations of adenylate cyclase. Divalent cations bound to the catalytic unit also affected the degree of synergism between hormone-activated Gs and forskolin to stimulate adenylate cyclase activity. In the presence of MgCl2 all effective doses of isoproterenol and forskolin in combination showed marked synergism. In contrast, with MnCl2 there was no synergism with high-dose isoproterenol-forskolin combinations, which gave only additive responses.
将氯化锰与氯化镁进行比较，观察它们在支持异丙肾上腺素、血管活性肠肽、氟化钠、鸟苷5'-（β，γ-亚氨基）三磷酸（GppNHp）或福斯可林对眼睫状体过程膜中腺苷酸环化酶系统的最大刺激方面的作用，以及在支持异丙肾上腺素和福斯可林之间的协同作用方面的表现。Mn2+（2 mM）的主要作用是由于其在催化单元上的相互作用。Mn2+对将β-肾上腺素能受体与腺苷酸环化酶催化单元偶联的GTP结合刺激性G蛋白（Gs）的功能没有显著影响。然而，当使用GppNHp代替GTP作为Gs蛋白的配体时，相对于Mg2+，Mn2+会损害Gs蛋白的功能。与Mg2+相比，Mn2+使腺苷酸环化酶对所有测试激活剂（GppNHp除外，其增加倍数为2.5 - 3.5倍）的反应性增加了4 - 5.5倍。因此，Mn2+离子似乎在控制其酶活性的催化单元上的二价阳离子结合位点处本质上更有效。睫状体过程膜不同于红细胞和S49淋巴瘤细胞膜，在后者中2 mM Mn2+会强烈抑制激素 - Gs蛋白介导的腺苷酸环化酶刺激。与催化单元结合的二价阳离子也影响激素激活的Gs和福斯可林之间刺激腺苷酸环化酶活性的协同程度。在MgCl2存在的情况下，所有有效剂量的异丙肾上腺素和福斯可林联合使用均显示出明显的协同作用。相比之下，使用MnCl2时，高剂量异丙肾上腺素 - 福斯可林组合没有协同作用，仅产生相加反应。
