Interactions between local anesthetics and spasmogens on the guinea-pig ileum.

The effect of various local anesthetics and other substances known to modify calcium fluxes in cells, on submaximal responses of guinea-pig ileum to substance P, acetylcholine, histamine and barium chloride was determined. Procaine caused a dose-related depression of the response to all the agonists but the response to substance P was far less susceptible to this depression. Lidocaine, bupivacaine, pramoxine and W 6211 also caused a lower degree of attenuation of the response to substance P than the responses to acetylcholine, histamine and barium chloride. Verapamil caused a dose-related depression of responses to all the agonists equally. The use of calcium-free solutions abolished responses to substance P, acetylcholine and histamine. The response to barium chloride was less affected by calcium withdrawal but was reduced markedly. In the presence of 10 mM lanthanum chloride, the response to all the agonists was abolished. The relative resistance of the substance P responses to antagonism by local anesthetics suggests that different and more efficient channels for calcium entry into the smooth muscle cell are involved.