Rius R A, Mollner S, Pfeuffer T, Loh Y P
Section on Cellular Neurobiology, National Institute of Child Health and Human Development, Bethesda, MD 20892.
Brain Res. 1994 Apr 18;643(1-2):50-8. doi: 10.1016/0006-8993(94)90007-8.
Guanine nucleotide-binding (G) proteins, Gs and G(olf) mediate the increase in cAMP formation through the activation of adenylyl cyclases. The developmental profiles of Gs, G(olf) and adenylyl were determined in mouse striatum and whole brain using immunobloting with specific antisera. Gs and the 115 kDa and 150 kDa adenylyl cyclases were present at the earliest age tested, embryonic day (E) 14.5 G(olf) and the 160 kDa adenylyl cyclase emerged in parallel, postnatally; during this period the increase in the relative abundance of the 150 kDa was observed. Gpp[NH]p activated Gs/G(olf) in a dose dependent manner, with a smaller response observed in embryos compared to adults. Mn2+ and forskolin activated the adenylyl cyclases and this activation increased during development. At E 14.5, maximal activation with Mn2+ and forskolin elicited a similar increase in cAMP levels, but from postnatal day 1, a nearly two fold higher response was obtained with forskolin compared to Mn2+; at the same time the 160 kDa adenylyl cyclase was detected. These data suggest that the appearance of certain forms of stimulatory G proteins was developmentally correlated with the expression of specific adenylyl cyclases.
鸟嘌呤核苷酸结合（G）蛋白Gs和G(olf) 通过激活腺苷酸环化酶介导环磷酸腺苷（cAMP）生成增加。利用特异性抗血清免疫印迹法，测定了小鼠纹状体和全脑中Gs、G(olf) 和腺苷酸环化酶的发育情况。最早在测试的胚胎期第14.5天（E14.5）就检测到了Gs以及115 kDa和150 kDa的腺苷酸环化酶。G(olf) 和160 kDa的腺苷酸环化酶在出生后同时出现；在此期间，观察到150 kDa的相对丰度有所增加。鸟苷酰亚胺二磷酸（Gpp[NH]p）以剂量依赖性方式激活Gs/G(olf)，与成年小鼠相比，胚胎中的反应较小。锰离子（Mn2+）和福斯可林激活腺苷酸环化酶，且这种激活在发育过程中增强。在E14.5时，Mn2+ 和福斯可林的最大激活引起cAMP水平类似的增加，但从出生后第1天开始，与Mn2+ 相比，福斯可林引起的反应高出近两倍；同时检测到160 kDa的腺苷酸环化酶。这些数据表明，某些形式的刺激性G蛋白的出现与特定腺苷酸环化酶的表达在发育上相关。
