Reduction of antigen-induced contraction of sensitized guinea-pig tracheal smooth muscle in vitro by calmodulin inhibitors.
The effect of two calmodulin inhibitors, 1-[bis(p-chlorophenyl)methyl]-3-[2,4-dichloro-beta-(2,4-dichlorobenzylox y) phenethyl]imidazolinium chloride (R 24571) and chlorpromazine (CPZ) on antigen-induced contraction of guinea-pig tracheal smooth muscle was studied. Ketotifen, an anti-allergic compound, was used as a comparative drug. Contraction of sensitized guinea-pig trachea induced by antigen challenge was reduced by all three agents. The two calmodulin inhibitors effected relaxation of contraction of guinea-pig trachea induced by histamine and leukotriene D4 (LTD4). Ketotifen relaxed histamine-induced contraction, but hardly affected LTD4-induced tone. Contrary to chemical mediator induced tone, all examined agents had no effect on resting tone. These three agents shifted histamine- and LTD4-induced concentration-contraction curves to the right. They produced a downward displacement of the maximum, without a parallel shift in histamine- and LTD4-induced concentration-contraction curves. The two calmodulin inhibitors did not affect the antigen-induced release of histamine and SRS-A from sensitized guinea-pig lung tissue. Ketotifen slightly inhibited the release of histamine. These results suggest that R 24571 and CPZ, calmodulin inhibitors, reduced an antigen-induced contraction of sensitized guinea-pig trachea in vitro mainly by affecting the contractility of tracheal smooth muscle by chemical mediators but not by interfering with the release of mediators.
D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002746:Chlorpromazine / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007114:Immunization; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D013189:SRS-A / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D000941:Antigens; D002147:Calmodulin; D007093:Imidazoles; D013189:SRS-A; C031938:calmidazolium; D006632:Histamine; D002746:Chlorpromazine; D007665:Ketotifen