β3-Adrenergic relaxation of bovine iris sphincter

Bovine iris sphincter in vitro responded to beta-adrenergic stimulation with pronounced relaxation (EC50 Of isoproterenol=0.3 nM), which was potentiated by the cAMP phosphodiesterase inhibitor, isobutylmethylxanthine, and mimicked by the adenylyl cyclase activator, forskolin, The beta(1)/beta(2) antagonist, propranolol, exhibited low potency with calculated K-i of 200 nM. The beta(3)-selective antagonist, bupranolol, exhibited a biphasic inhibition profile, with calculated K(i)s of approximately 20-50 and 200-300 nM. The beta(3)-selective agonist, BRL 37344, elicited 70% of maximal relaxation (EC50=30 nM), When relaxation was induced by BRL 37344, bupranolol exhibited much higher potency (calculated K-i = 1 nM). Our data suggest that the beta-adrenergic relaxation response in bovine iris sphincter is mediated by a mixed population of beta-adrenergic receptors, with a predominant contribution of atypical, most likely beta(3) subtype, receptors. (C) 1998 Federation of European Biochemical Societies.