Effects of calcium-entry modulators on the biphasic neurogenic contractions in the circular muscle of guinea pig vas deferens.

Abstract

Effects of nifedipine (10(-8)-10(-6) M), verapamil (10(-6)-3 x 10(-5) M) and Bay k 8644 (10(-7) M) on the contractions induced by transmural nerve stimulation or agonists were investigated in the circular smooth muscle of guinea pig vas deferens using a ring preparation. Transmural stimulation (20 Hz for 20 sec) produced biphasic contractions consisting of initial phasic and secondary tonic components. Nifedipine preferentially inhibited the tonic component and norepinephrine (NE)-induced contractions over the phasic component and beta, gamma-methylene ATP (mATP)-induced contractions. Nifedipine suppressed the enhancing effect of NE on the mATP-induced contractions. The tonic component and NE-induced contractions were inhibited by verapamil in a similar dose range. Verapamil slightly inhibited the phasic component, but rather enhanced mATP-induced contractions. Bay k 8644 slightly increased the phasic component and mATP-induced contractions in the presence of prazosin. Bay k 8644 slowed the relaxation of the tonic component, thereby prolonging the tonic component. Bay k 8644 also prolonged the duration of NE-induced contractions. These results, except for the contradictory effects of verapamil between the phasic component and mATP-induced contractions, are consistent with the claim that ATP and NE are responsible for the generation of phasic and tonic component, respectively, in the circular muscle of guinea pig vas deferens.