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. CONCLUSION: 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.
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 bovineiris 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 bovineiris 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. CONCLUSION: 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.
Authors: Philippa R Dale; Hana Cernecka; Martina Schmidt; Mark R Dowling; Steven J Charlton; Michael P Pieper; Martin C Michel Journal: Curr Opin Pharmacol Date: 2014-03-27 Impact factor: 5.547
Authors: Subramanian Senthilkumaran; Namasivayam Balamurugan; Ritesh G Menezes; Ponniah Thirumalaikolundusubramanian Journal: Indian J Crit Care Med Date: 2014-07