McMahon K K, Hosey M M
Biochem Biophys Res Commun. 1983 Feb 28;111(1):41-6. doi: 10.1016/s0006-291x(83)80114-4.
Guanine nucleotides and monovalent cations decrease the affinity of cardiac muscarinic receptors for agonists and are required for muscarinic receptor mediated inhibition of adenylate cyclase. N-ethylmaleimide abolished the effects of Gpp(NH)p on the ability of the agonist oxotremorine to inhibit the binding of the antagonist [3H]quinuclidinyl benzilate to purified chick heart membranes. However, the effects of NH4+ to decrease the IC50 for oxotremorine were retained in N-ethylmaleimide treated membranes. The N-ethylmaleimide treatment mimicked the effects of Gpp(NH)p and the oxotremorine inhibition curves obtained with treated membranes in the presence of NH4+ were identical to those obtained in control membranes in the presence of NH4+ and Gpp(NH)p. The results suggest that monovalent cation effects on muscarinic receptors are mediated at a site distinct from effects produced by guanine nucleotides and are greater on free receptors than on receptors coupled to guanine nucleotide binding proteins.
鸟嘌呤核苷酸和单价阳离子可降低心肌毒蕈碱受体对激动剂的亲和力，且是毒蕈碱受体介导的腺苷酸环化酶抑制作用所必需的。N-乙基马来酰亚胺消除了Gpp(NH)p对激动剂氧化震颤素抑制拮抗剂[3H]喹核醇基苯甲酸酯与纯化的鸡心膜结合能力的影响。然而，在N-乙基马来酰亚胺处理的膜中，NH4+降低氧化震颤素IC50的作用仍然存在。N-乙基马来酰亚胺处理模拟了Gpp(NH)p的作用，并且在存在NH4+的情况下，用处理过的膜获得的氧化震颤素抑制曲线与在存在NH4+和Gpp(NH)p的对照膜中获得的曲线相同。结果表明，单价阳离子对毒蕈碱受体的作用是在一个与鸟嘌呤核苷酸产生的作用不同的位点介导的，并且对游离受体的作用比对与鸟嘌呤核苷酸结合蛋白偶联的受体的作用更大。
