Takayanagi I, Koike K, Satoh M
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Nihon Yakurigaku Zasshi. 1992 Oct;100(4):279-92. doi: 10.1254/fpj.100.279.
It is generally accepted that full and partial agonists interact with the same receptors according to the classical receptor mechanisms. We have modified the drug receptor mechanisms of M3-, alpha 1- and beta-receptors. Among the muscarinic receptors, there are two subtypes of M3-cholinoceptors, propylbenzilylcholine mustard (PrBCM)-sensitive receptors and (PrBCM)-resistant ones. Full agonists contract the guinea pig ileum through both types of cholinoceptors, while the partial agonists produce contractions through only the PrBCM-sensitive receptors. Two subtypes of alpha 1-adrenoceptors, alpha 1A and alpha 1B, were demonstrated in some arteries. Full agonists contracted the rabbit aorta through both the alpha 1A- and alpha 1B-adrenoceptors, while the partial agonists mediated contraction through only the alpha 1A-adrenoceptors. beta-Chloroethylamines (PrBCM and chloroethylclonidine) can discriminate the subtype of M3- or alpha 1-receptors in the presence of GTP. beta-Adrenoceptors have two different types of binding sites, high and low affinity sites. The competitive antagonistic effect of the partial agonist is due to their ability to compete with the full agonists for the high affinity site, while the partial agonists interact with the low affinity site to induce the beta-adrenergic effect. A regional difference in alpha 1-adrenoceptor mechanisms was discussed. The potency of norepinephrine in veins is related to alpha 1-adrenoceptor densities. In contrast, the potency of norepinephrine is linearly related to the agonist dissociation constant. This discrepancy suggests a qualitative difference between alpha 1-adrenoceptor mechanisms in the veins and arteries.
一般认为，完全激动剂和部分激动剂根据经典受体机制与相同的受体相互作用。我们已经对M3、α1和β受体的药物受体机制进行了修改。在毒蕈碱受体中，有两种M3胆碱能受体亚型，即对丙基苄基胆碱氮芥（PrBCM）敏感的受体和对（PrBCM）耐药的受体。完全激动剂通过两种胆碱能受体使豚鼠回肠收缩，而部分激动剂仅通过对PrBCM敏感的受体产生收缩。在一些动脉中证实了α1肾上腺素能受体的两种亚型，即α1A和α1B。完全激动剂通过α1A和α1B肾上腺素能受体使兔主动脉收缩，而部分激动剂仅通过α1A肾上腺素能受体介导收缩。在存在GTP的情况下，β-氯乙胺（PrBCM和氯乙可乐定）可以区分M3或α1受体的亚型。β肾上腺素能受体有两种不同类型的结合位点，即高亲和力位点和低亲和力位点。部分激动剂的竞争性拮抗作用是由于它们能够与完全激动剂竞争高亲和力位点，而部分激动剂与低亲和力位点相互作用以诱导β-肾上腺素能效应。讨论了α1肾上腺素能受体机制的区域差异。去甲肾上腺素在静脉中的效力与α1肾上腺素能受体密度有关。相反，去甲肾上腺素的效力与激动剂解离常数呈线性关系。这种差异表明静脉和动脉中α1肾上腺素能受体机制存在质的不同。
