Reddy R, Smith D, Wayman G, Wu Z, Villacres E C, Storm D R
Department of Pharmacology, University of Washington, Seattle 98195, USA.
J Biol Chem. 1995 Jun 16;270(24):14340-6. doi: 10.1074/jbc.270.24.14340.
Catalytic subunits of mammalian adenylyl cyclases have been proposed to contain 12 transmembrane domains, a property shared with some voltage-sensitive ion channels. Here we report that adenylyl cyclase activity in cerebellar neurons is synergistically stimulated by depolarizing agents and beta-adrenergic receptor activation. This phenomenon is Ca(2+)-independent and not attributable to Ca(2+)-stimulated adenylyl cyclase activity. Cholera toxin and forskolin also synergistically stimulate adenylyl cyclase activity in combination with depolarizing agents. We hypothesize that conformational changes in the catalytic subunit of the enzymes caused by changes in the membrane potential may enhance stimulation of adenylyl cyclases by the guanylyl nucleotide stimulatory protein. This novel mechanism for regulation of adenylyl cyclases generates robust cAMP signals that may contribute to various neuromodulatory events including some forms of neuroplasticity.
哺乳动物腺苷酸环化酶的催化亚基被认为含有12个跨膜结构域，这一特性与一些电压敏感离子通道相同。在此我们报告，小脑神经元中的腺苷酸环化酶活性受到去极化剂和β-肾上腺素能受体激活的协同刺激。这种现象不依赖于Ca(2+)，也不能归因于Ca(2+)刺激的腺苷酸环化酶活性。霍乱毒素和福斯高林与去极化剂联合使用时也能协同刺激腺苷酸环化酶活性。我们推测，膜电位变化引起的酶催化亚基构象变化可能会增强鸟苷酸刺激蛋白对腺苷酸环化酶的刺激作用。这种调节腺苷酸环化酶的新机制产生强大的cAMP信号，可能有助于各种神经调节事件，包括某些形式的神经可塑性。
