Gallamine allosterically antagonizes muscarinic receptor-mediated inhibition of adenylate cyclase activity in the rat myocardium.
Gallamine allosterically antagonizes muscarinic receptor-mediated inhibition of adenylate cyclase activity in the rat myocardium.
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Gallamine 变构拮抗毒蕈碱受体介导的大鼠心肌腺苷酸环化酶活性抑制。
DOI：
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发表时间：
1988
影响因子：
3.5
通讯作者：
F. Ehlert
中科院分区：
文献类型：
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作者：
F. Ehlert
在大鼠心肌中研究了没食子酸胺修饰毒蕈碱受体结合特性和拮抗毒蕈碱受体介导的腺苷酸环化酶活性抑制的能力。在抑制腺苷酸环化酶活性的剂量-反应曲线中，由高效毒蕈碱激动剂oxotremorine-M和部分激动剂Bm 5 [N-甲基-N-（1-甲基-4-吡咯烷基）-2-丁炔基乙酰胺]引起的剂量-反应曲线向右平行移动。这种效应的性质与竞争性抑制不一致，但可以用变构拮抗作用来解释。估计类似的解离常数为0.52和0.83 μ M的基础上，它的能力，以拮抗反应oxotremorine-M和BM 5，分别为加拉胺。Bm 5的剂量-反应曲线的最大移动由gallamine引起的是90倍，而oxotremorine-M的只有49倍。当通过抑制特异性毒蕈碱拮抗剂[3 H] N-甲基东莨菪碱的结合来测量时，估计没食子胺的解离常数为1.1 μ M。本研究结果表明，良好的协议之间的能力，没食子胺修改毒蕈碱受体结合特性和拮抗毒蕈碱受体介导的抑制腺苷酸环化酶活性在大鼠心脏。
The ability of gallamine to modify muscarinic receptor binding properties and to antagonize muscarinic receptor-mediated inhibition of adenylate cyclase activity was investigated in the rat myocardium. Gallamine caused parallel shifts to the right in the dose-response curves for inhibition of adenylate cyclase activity by the highly efficacious muscarinic agonist oxotremorine-M and the partial agonist Bm 5 [N-methyl-N-(1-methyl-4-pyrrolidino)-2-butynyl acetamide]. The nature of this effect was inconsistent with competitive inhibition, but could be explained by allosteric antagonism. Similar dissociation constants of 0.52 and 0.83 microM were estimated for gallamine on the basis of its ability to antagonize responses to oxotremorine-M and Bm 5, respectively. The maximum shift in the dose-response curve of Bm 5 caused by gallamine was 90-fold, whereas that of oxotremorine-M was only 49-fold. When measured by inhibition of the binding of the specific muscarinic antagonist [3H]N-methylscopolamine, the dissociation constant of gallamine was estimated to be 1.1 microM. The present results illustrate good agreement between the ability of gallamine to modify muscarinic receptor binding properties and to antagonize muscarinic receptor-mediated inhibition of adenylate cyclase activity in the rat heart.