INTERACTIONS BETWEEN LOCAL-ANESTHETICS AND SPASMOGENS ON GUINEA-PIG ILEUM

Abstract

The effect of various local anesthetics and other substances which are known to modify Ca fluxes in cells was determined on submaximal responses of guinea-pig ileum to substance P, acetylcholine, histamine and BaCl2. 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 [a lidocaine analog] also caused a lower degree of attenuation of the response to substance P than the responses to acetylcholine, histamine and BaCl2. Verapamil caused a dose-related depression of responses to all the agonists equally. The use of Ca-free solutions abolished responses to substance P, acetylcholine and histamine. The response to BaCl2 was less affected by Ca withdrawal but was reduced markedly. In the presence of 10 mM LaCl2, 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 Ca entry into the smooth muscle cell are involved.