Beta3-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 beta1/beta2 antagonist, propranolol, exhibited low potency with calculated Ki of 200 nM. The beta3-selective antagonist, bupranolol, exhibited a biphasic inhibition profile, with calculated Kis of approximately 20-50 and 200-300 nM. The beta3-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 Ki = 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 beta3 subtype, receptors.
Geyer
O
O
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Bar-Ilan
A
A
Nachman
R
R
Lazar
M
M
Oron
Y
Y
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D002046:Bupranolol / Q000494:pharmacology; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology; D007498:Iris / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D009126:Muscle Relaxation / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D005576:Colforsin; C057368:BRL 37344; D002046:Bupranolol; D000242:Cyclic AMP; D007545:Isoproterenol; D000420:Albuterol