The effect of nifedipine on the contractile responses of the longitudinal and circular muscle of the isolated guinea-pig ileum to various agonists.

We investigated the inhibitory effect of nifedipine on contractile responses of the longitudinal and circular muscle of the isolated guinea-pig ileum. Nifedipine in very low concentrations, ranging from picomolar to nanomolar, inhibits the phasic and the tonic contractile responses of the longitudinal muscle induced by various agonists (histamine, acetylcholine, prostaglandin E2, serotonin and potassium chloride) in a concentration-dependent manner. Nifedipine produces a stronger inhibition of the tonic than of the phasic component of contractions induced by used spasmogens. The tonic contractile responses evoked by histamine and acetylcholine exhibited the highest degree of sensitivity to the inhibitory action of nifedipine. The calculated values of mean effective concentrations (ED50) indicate that the phasic responses of agonists are less sensitive to nifedipine. For obtaining a similar degree of inhibition of phasic contractions much higher concentrations of nifedipine are necessary. Our findings that nifedipine inhibits more strongly the tonic than the phasic contractile responses produced by different agonists, support the hypothesis of the existence of various types of calcium channels in the guinea-pig longitudinal muscle. Also, nifedipine reduced the contractile responses of the ileal circular muscle induced by histamine, acetylcholine, prostaglandin E2, serotonin and potassium chloride, in a concentration-dependent manner. The contractions induced by histamine are most sensitive to the inhibitory action of nifedipine. It should be pointed out that the phasic responses of the longitudinal muscle and contractions of the circular muscle are approximately equally sensitive to nifedipine. It can be speculated that some inherent similarity exists in contractile processes of the phasic responses of the longitudinal muscle and contractions of the circular muscle, or that agonists act via the same (or similar) population of calcium channels. Enhancing the calcium concentration in the bathing fluid did not reverse the inhibitory effect of nifedipine on contractions of the longitudinal and circular muscle, induced by various agonists.