Antagonism of the uterotonic action of oxytocin in vitro.
Cumulative concentration-effect curves of oxytocin alone and with various antagonists were obtained in vitro on uteri from estrogen-treated rats.  Graded concentrations of salbutamol, isoproterenol, papaverine, theophylline, thioglycollate, and MgCl2 produced a decrease in the maximal effect of oxytocin and a shift of the concentration-effect curves to the right.  Salbutamol and isoproterenol appeared to act as functional antagonists of oxytocin in which agonist and antagonist each interacted with its own specific receptor to produce a decreased combined effect on a common effector.  Antagonism by papaverine or theophylline was increased by prior or simultaneous treatment with salbutamol, isoproterenol, epinephrine, or norepinephrine.  The potentiation had a rapid onset, was partially blocked by propranolol, persisted for at least 85 minutes following washout of salbutamol, and was not due to a residual effect of salbutamol.  This interaction could result from phosphodiesterase inhibition by papaverine and the accumulation of higher levels of cyclic 3',5'-adenosine monophosphate brought about by adenyl cyclase activation with the sympathomimetic amines.
D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D004357:Drug Synergism; D004837:Epinephrine; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009638:Norepinephrine; D010121:Oxytocin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D013806:Theophylline / Q000494:pharmacology; D013864:Thioglycolates / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects*
D009125:Muscle Relaxants, Central; D013864:Thioglycolates; D010121:Oxytocin; D011433:Propranolol; D013806:Theophylline; D010208:Papaverine; D008274:Magnesium; D007545:Isoproterenol; D000420:Albuterol; D009638:Norepinephrine; D004837:Epinephrine