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首页> 外文期刊>Life sciences >Pharmacological evaluation of ocular beta-adrenoceptors in rabbit by tissue segment binding method.
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Pharmacological evaluation of ocular beta-adrenoceptors in rabbit by tissue segment binding method.

机译：组织片段结合法测定家兔眼β-肾上腺素受体的药理作用。

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AIMS: This study evaluates ocular (iris, ciliary body and ciliary process) and nonocular (atria and lung) beta-adrenoceptors in rabbit to characterize the plasma membrane beta-adrenoceptors and binding affinities of beta-adrenoceptor antagonists. MAIN METHODS: The tissue segment binding method with a hydrophilic radioligand (-)-4-[3-t-butylamino-2-hydroxypropoxy]-[5,7-(3)H]benzimidazol-2-one ([(3)H]-CGP12177) was employed. KEY FINDINGS: Specific and saturable binding of [(3)H]-CGP12177 to intact tissue segments was detected by using (+/-)-propranolol to define nonspecific binding, showing a single population of plasma membrane binding sites with high affinity. Competition experiments with selective beta(1)- and beta(2)-adrenoceptor antagonists revealed a single population of beta(2)-adrenoceptors in ocular tissues and of beta(1)-adrenoceptors in atria, but mixed populations of beta(1)- and beta(2)-adrenoceptors in 70% and 30%, respectively, in lung. A competition curve for timolol was biphasic in lung and its binding affinity for beta(2)-adrenoceptors was approximately 158-fold higher than for beta(1)-adrenoceptors, indicating the beta(2)-selectivity of timolol. In contrast, competition curves for stereoisomers of befunolol, carteolol, and propranolol were monophasic in all tissues. The (-)-enantiomers of these antagonists were more potent than corresponding (+)-enantiomers in displacing from [(3)H]-CGP12177 binding, and the isomeric potency ratios of befunolol and carteolol were less than those of propranolol. SIGNIFICANCE: This study with tissue segment binding method suggests that the binding affinity of (-)-enantiomers of beta-adrenoceptor antagonists for plasma membrane beta-adrenoceptors (beta(1)-adrenoceptors of atria, beta(2)-adrenoceptors of ocular tissues, and mixed beta(1)-/beta(2)-adrenoceptors of lung) is higher than that of corresponding (+)-enantiomers and their stereoselectivity is different between beta-adrenoceptor antagonists.
机译：目的：本研究评估了兔子的眼（虹膜，睫状体和睫状突）和非眼（心房和肺）β-肾上腺素受体，以表征质膜β-肾上腺素受体和β-肾上腺素受体拮抗剂的结合亲和力。主要方法：用亲水性放射性配体（-）-4- [3-t-丁基氨基-2-羟基丙氧基]-[5,7-（3）H]苯并咪唑-2-one（[（3）使用H] -CGP12177）。主要发现：[（3）H] -CGP12177与完整组织片段的特异性和饱和结合是通过使用（+/-）-普萘洛尔定义非特异性结合来检测的，显示出具有高亲和力的单质膜结合位点群体。选择性β（1）-和β（2）-肾上腺素受体拮抗剂的竞争实验显示，眼组织中存在单个β-（2）-肾上腺素受体群，心房中存在β（1）-肾上腺素受体群，但是β（1）的混合群-和β（2）-肾上腺素受体分别在肺中占70％和30％。噻吗洛尔的竞争曲线在肺部是双相的，其对β（2）-肾上腺素受体的结合亲和力比对β（1）-肾上腺素受体高约158倍，表明噻吗洛尔的β（2）-选择性。相反，在所有组织中，倍福洛尔，卡特洛尔和普萘洛尔的立体异构体的竞争曲线都是单相的。这些拮抗剂的（-）-对映异构体在取代[（3）H] -CGP12177结合方面比相应的（+）-对映异构体更有效，并且倍福洛尔和卡特洛尔的异构效价比低于普萘洛尔。意义：这项利用组织节段结合方法的研究表明，β-肾上腺素受体拮抗剂的（-）-对映体对质膜β-肾上腺素受体（β（1）-心房肾上腺素受体，β（2）-眼组织肾上腺素受体）的结合亲和力，并且混合的β（1）-/β（2）-肺肾上腺素受体比相应的（+）-对映体高，并且它们的立体选择性在β-肾上腺素受体拮抗剂之间是不同的。

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