Takayanagi I, Koike K, Satoh M, Okayasu A
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Jpn J Pharmacol. 1997 Jan;73(1):1-22. doi: 10.1254/jjp.73.1.
Both alpha1-adrenoceptors and M3-cholinoceptors can be divided into two subtypes discriminated by the beta-chloroethylamines, chloroethylclonidine and propylbenzilylcholine mustard (PrBCM), only in the presence of GTP. The full agonists interact with both subtypes to induce responses. The partial agonists activate one of them to induce responses but behave as competitive antagonists when they interact with the other. The responses mediated through the receptors that are activated by the partial agonists are resistant to myosin light chain kinase inhibitors, while the response through the activation of the other receptors are suppressed by the inhibitors. The receptor stimulations through alpha1A-adrenoceptor and PrBCM-sensitive M3-cholinoceptor subtypes mainly activate the myosin light chain-phosphorylation-independent pathway mediated through protein kinase C and low molecular weight GTP-binding protein, whereas the stimulations through alpha1B-adrenoceptors and the PrBCM-phosphorylation-dependent pathway are directly related to Ca2+/calmodulin.
仅在存在鸟苷三磷酸（GTP）的情况下，α1肾上腺素能受体和M3胆碱能受体均可分为由β-氯乙胺、氯乙可乐定和丙基苯甲酰胆碱氮芥（PrBCM）区分的两种亚型。完全激动剂与两种亚型相互作用以诱导反应。部分激动剂激活其中一种亚型以诱导反应，但当它们与另一种亚型相互作用时表现为竞争性拮抗剂。通过部分激动剂激活的受体介导的反应对肌球蛋白轻链激酶抑制剂具有抗性，而通过激活其他受体介导的反应则被这些抑制剂抑制。通过α1A肾上腺素能受体和PrBCM敏感的M3胆碱能受体亚型的受体刺激主要激活通过蛋白激酶C和低分子量GTP结合蛋白介导的不依赖肌球蛋白轻链磷酸化的途径，而通过α1B肾上腺素能受体的刺激和PrBCM磷酸化依赖性途径则与Ca2+/钙调蛋白直接相关。
