β₃-Adrenergic relaxation of bovine iris sphincter

Bovine iris sphincter in vitro responded to β-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 β₁/β₂ antagonist, propranolol, exhibited low potency with calculated K(i) of 200 nM. The β₃-selective antagonist, bupranolol, exhibited a biphasic inhibition profile, with calculated K(i)s of approximately 20-50 and 200-300 nM. The β₃-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 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 β₃ subtype, receptors.