Muscarinic blockers potentiate beta-adrenergic relaxation of bovine iris sphincter.
BACKGROUND
beta-Adrenergic relaxation of iris sphincter has been described in many species, including human. It is generally accepted that the size of the pupil is mainly controlled by muscarinic and alpha-adrenergic tonus. This study was undertaken to investigate the interactions between muscarinic and beta-adrenergic drugs in the relaxation of bovine iris sphincter.


METHODS
Intact bovine iris sphincters were incubated in an organ bath and challenged with appropriate beta-adrenergic agonists and/or muscarinic antagonists. Tension was measured by a force transducer.


RESULTS
Isolated bovine iris sphincter responded to muscarinic stimulation by contraction and to beta-adrenergic stimulation by relaxation. The beta-adrenergic agonists isoproterenol (ISO) and salbutamol (SAL) each caused marked relaxation of sphincters pre-contracted with the muscarinic agonist carbamylcholine. Sphincters pre-treated with the muscarinic antagonists atropine (0.1 micro M) or ipratropium bromide (10 micro M) and challenged 5 min later with either isoproterenol (0.3 nM) or salbutamol (10 nM) exhibited approximately twofold potentiation of beta-adrenergic relaxation. Adding the drugs in the reverse order did not produce any potentiation over the effect of beta-adrenergic stimulation alone. The dose-response curve to isoproterenol in naive sphincters or sphincters pre-treated with atropine indicated that muscarinic blockade decreased the EC(50) rather than potentiated maximal beta-adrenergic relaxation.


CONCLUSIONS
Muscarinic antagonists potentiate beta-adrenergic relaxation of the sphincter by affecting the apparent potency of beta-adrenergic agonists and not by antagonizing the intrinsic tonus produced by endogenously released acetylcholine.
Barilan
Ayelet
A
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Nachman-Rubinstein
Rachel
R
Oron
Yoram
Y
Geyer
Orna
O
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007498:Iris / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D018727:Muscarinic Antagonists; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D007545:Isoproterenol; D000420:Albuterol