β 3-Adrenergic relaxation of bovine iris sphincter

Abstract

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