INFLUENCE OF CHLORPROMAZINE ON CALCIUM MOVEMENTS AND CONTRACTILE RESPONSES OF GUINEA-PIG ILEUM LONGITUDINAL SMOOTH-MUSCLE TO AGONISTS

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  • 1 January 1978
    • journal article
    • research article
    • Vol. 236  (1) , 109-124
Abstract
The effects of chlorpromazine (CPZ) on the uptake and release of Ca 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 Ca uptake of the microsomes by 85-95%, and increased the release of preloaded Ca from the microsomes from 5% to 40% in the first 5 min. CPZ-induced Ca release was increased by chelating agents [ethyleneglycolbis (.beta.-aminoethyl)-N,N-tetraacetic acid and disodium ethylenediaminetetraacetate], KCl and NaCl. These agents increased the CPZ-induced Ca release from 40% in the first 5 min to an average of 87% in the first 5 min. CPZ-induced Ca release was inhibited by CaCl2. CPZ (1-10 .mu.M) 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 and shown to be reversed by CaCl2 (9.8 mM). CPZ appears to interfere at 1-10 .mu.M levels with Ca movements of the sarcolemma and in vitro at 0.5-1 mM levels with Ca movements of isolated sarcoplasmic reticulum.