Influence of chlorpromazine on calcium movements and contractile responses of guinea-pig ileum longitudinal smooth muscle to agonists.

The effects of chlorpromazine (CPZ) on the uptake and release of calcium by microsomes prepared from longitudinal smooth muscle of guinea-pig ileum (GPI) in vitro and on contractions of longitudinal muscle of GPI in situ to various agonists were studied. CPZ (0.5-1 mM) blocked calcium uptake of the microsomes by 85-95%, and increased the release of preloaded calcium from the mocrosomes from 5% to 40% in the first 5 min. CPZ-induced calcium release was increased by chelating agents [ethyleneglycolbis (beta-amino-ethyl)-N, N-tetraacetic acid and disodium ethylenediaminetetraacetate], KCL and NaCl. These agents increased the CPZ-induced calcium release from 40% in the first 5 min to an average of 87% in the first 5 min. CPZ-induced calcium release was inhibited by CaCl2. CPZ (1-10 micrometer) decreased contractile responses of muscle strips to low and high levels of contractile agonists. These agonists were 5-methylfurmethide (an analog of muscarine), 5-hydroxytryptamine, histamine, BaCl2 and KCl. CPZ moved the dose-response curves to the right and depressed maximal responses. KCl-induced contractions when blocked by CPZ were tested for the shown to be reversed by CaCl2 (9.8 mM). CPZ appears to interfere at 1-10 micrometer levels with calcium movements of the sarcolemma and in vitro at 0.5-1 mM levels with calcium movements of isolated sarcoplasmic reticulum.