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.