Effect of diphenylhydantoin on drug and calcium induced contractions of isolated rat uterus: a comparative study with nifedipine.
The sustained contractions induced by K+, acetylcholine (ACh) and oxytocin (Ot) were inhibited in a concentration-dependent fashion by diphenylhydantoin (DPH) and nifedipine (NIF) in the following order of sensitivity: K+ greater than ACh greater than Ot. Previous incubation of DPH and NIF produced a non-competitive antagonism towards ACh and Ot-induced contractions. Increasing of calcium (Ca2+) concentration (0.2-1.5 mM) completely reverse the inhibitory effect of DPH and NIF, suggesting a competitive type of antagonism, between Ca2+ and DPH. A clear difference between DPH and NIF actions was observed when the K+-depolarizing solution was used. In this condition, DPH caused a parallel and concentration-related rightward displacement of the dose-response curves of Ca2+ (pA2 = 4.91 +/- 0.1), while NIF produced a rightward displacement allied to a significant reduction of the Ca2+ maximal response. DPH, but not NIF, produced a concentration-dependent relaxation in sustained contraction induced by Ca2+ (1 mM) in depolarized tissue.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology*; D010121:Oxytocin / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors; D014590:Uterine Contraction / Q000187:drug effects*
D007473:Ion Channels; D010121:Oxytocin; D010672:Phenytoin; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium