Avissar S, Schreiber G
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892.
FEBS Lett. 1990 Jan 15;260(1):95-7. doi: 10.1016/0014-5793(90)80075-t.
The specific mechanism by which the inhibitory guanine nucleotide binding protein (Gi) mediates the inhibition of adenylate cyclase activity is still unclear. The subunit dissociation model, based on studies in purified or reconstituted systems, suggests that the beta gamma subunit, which is dissociated with activation of Gi, inhibits the function of the stimulatory guanine nucleotide binding protein (Gs) by reducing the concentration of the free alpha s subunit. In the present study, Gs protein function is determined by measuring cholera toxin-blockable, isoproterenol-induced increases in guanosine triphosphate (GTP) binding capacity to rat cardiac ventricle membrane preparations. Carbamylcholine totally inhibited this beta-adrenergic receptor-coupled Gs protein function. Pretreatment of the cardiac ventricle membrane with pertussis toxin prevented this muscarinic agonist effect. These results confirm the possibility of an inhibitory agonist-receptor coupled effect through Gi on Gs protein function proximal to the catalytic unit of adenylate cyclase in an intact membrane preparation.
抑制性鸟嘌呤核苷酸结合蛋白（Gi）介导腺苷酸环化酶活性抑制的具体机制仍不清楚。基于对纯化或重组系统的研究，亚基解离模型表明，与Gi激活相关的βγ亚基通过降低游离αs亚基的浓度来抑制刺激性鸟嘌呤核苷酸结合蛋白（Gs）的功能。在本研究中，通过测量霍乱毒素可阻断的、异丙肾上腺素诱导的大鼠心室膜制剂中鸟苷三磷酸（GTP）结合能力的增加来确定Gs蛋白功能。氨甲酰胆碱完全抑制了这种β-肾上腺素能受体偶联的Gs蛋白功能。用百日咳毒素预处理心室膜可阻止这种毒蕈碱激动剂的作用。这些结果证实了在完整膜制剂中，通过Gi对腺苷酸环化酶催化单元近端的Gs蛋白功能产生抑制性激动剂-受体偶联效应的可能性。
