Pharmacological characterization of human ciliary muscle adrenoceptors in vitro

Abstract

The in vitro pharmacological characteristics of adrenoceptors of the human ciliary muscle were investigated. Tissue was obtained from 30 eyes used previously for corneal transplantations which had been enucleated 6-24 hr after death. Experiments were performed within 2 days of enucleation. Strips of the meridional and circular portion of the ciliary muscle were attached to a tension gauge in an organ bath and the effect of drugs added to the perfusion medium was monitored isometrically. The muscle was precontracted with physostigmine (10(-5) M) and acetylcholine (10(-5) M). The non-selective beta adrenoceptor agonist isoproterenol (10(-6)-10(-3) M) caused a dose-related relaxation of the ciliary muscle, an effect which was completely inhibited by the non-selective beta adrenoceptor antagonist timolol (10(-5) M), while the beta 1 adrenoceptor antagonist betaxolol (10(-5) M) had no effect. The beta 2 adrenoceptor agonist salbutamol (10(-6)-10(-3) M) produced a dose-related relaxation of the ciliary muscle, an effect which was completely blocked by the beta 2 adrenoceptor antagonist L1 32-468 (10(-5) M). The non-selective alpha adrenoceptor agonist noradrenaline (10(-6)-10(-3) M) also caused a dose-related relaxation of the ciliary muscle. The non-selective alpha adrenoceptor antagonists phentolamine (10(-5) M) and thymoxamine (10(-5) M) and the alpha 1 adrenoceptor antagonist prazosin (10(-5) M) partially blocked the response to noradrenaline, while the alpha 2 adrenoceptor antagonist idazoxan (10(-5) M) and timolol (10(-5) M) had no effect. The alpha 1 adrenoceptor agonist phenylephrine (5 X 10(-6)-5 X 10(-3) M) caused a dose-dependent relaxation in five out of 12 isoproterenol-sensitive muscle strips. Further, it was not possible to block the phenylephrine-induced relaxation with thymoxamine (10(-5) M). The alpha 2 adrenoceptor agonist clonidine (10(-6)-10(-3) M) had no effect. No qualitative difference between drug effects on the meridional and circular ciliary muscles was observed. We conclude from these data that beta 2, and most probably alpha 1, adrenoceptors are present on both the meridional and circular portions of the ciliary muscle of the human eye.