Diphenylhydantoin inhibition of drug-induced contractions of isolated rat vas deferens: additional evidence for a calcium-blocking action.
The present study analyzed the inhibitory effects of diphenylhydantoin (DPH) on acetylcholine (Ach)-, norepinephrine (NE)- and 5-hydroxytryptamine (5-HT)-induced contractions of the isolated rat vas deferens in normal bath medium. The effect of DPH on CaCl2-induced contractions of depolarized preparations was also investigated. Pre-incubation with 30 microM to 1mM DPH for 20 min promoted a non-competitive antagonism of Ach-, 5-HT- and NE-induced contractions with pD'2 values of 4.0 +/- 0.11, 4.05 +/- 0.10 and 3.38 +/- 0.10, respectively. In contrast, 12.5 microM to 100 microM DPH caused parallel, dose-related, rightward displacements of the dose-response curve to CaCl2 in potassium depolarizing solution. The Schild plot of these data was linear and compatible with a competitive antagonism by DPH of Ca2+-induced contractions (pA2 = 4.75 +/- 0.2; slope = 0.99). These results strongly suggest that, in the isolated rat vas deferens, DPH interferes competitively with Ca2+ membrane translocation, thus inhibiting the action of several neurotransmitters in a non-competitive manner.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D010672:Phenytoin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects*
D012701:Serotonin; D010672:Phenytoin; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine