Chlorpromazine at comparatively low concentrations potentiates carbachol-induced tonic contraction of ileal longitudinal smooth muscle of the guinea-pig.
The neuroleptic phenothiazine derivative chlorpromazine (CPZ) at high concentration (1 x 10(-5) M) decreased either the phasic or tonic contraction in response to carbachol and the carbachol-induced increase in [Ca2+]i in both phases in ileal muscle. In contrast, CPZ at low concentrations (8 x 10(-7) - 5 x 10(-6) M) decreased only the phasic contraction and potentiated the tonic contraction induced by carbachol. However, CPZ at these concentrations dose-dependently decreased the carbachol-induced increase in [Ca2+]i in both phases. These results suggested that CPZ dose-dependently decreased the initial phasic contraction in response to carbachol by inhibition of Ca2+ release from the intracellular storage sites. CPZ at low concentrations appears to increase Ca2+ sensitivity to contractile proteins in the carbachol-induced tonic phase. CPZ dose-dependently reduced the 60 mM K(+)-induced phasic and tonic responses and a concomitant decrease in [Ca2+]i in ileal muscle.
Nasu
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Department of Veterinary Pharmacology, Faculty of Agriculture, Yamaguchi University, Yamaguchi 753, Japan. nasu@agr.yamaguchi-u.ac.jp
Ou
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D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*
D014150:Antipsychotic Agents; D002217:Carbachol; D002746:Chlorpromazine