A study of the mode and site of action of capsaicin in guinea-pig heart and rat uterus.
Capsaicin (CAP) has been shown to exert a selective neurotoxic effect on peptidergic primary afferent neurons. The effect of CAP on the isolated guinea-pig left auricle and papillary muscle preparations and on the isolated rat uterus was used to elucidate its mode and site of action with regard to cellular Ca2+ utilization. In the electrically driven left auricle CAP first increased and then decreased the size of the contractions while in the electrically driven papillary muscle CAP caused only a decrease in the contractions. Electrophysiological measurements showed that the initial increase in contraction size coincided with a decrease in the upstroke velocity of the action potential. This membrane-stabilizing effect of CAP seemed also responsible for the decrease in contractile activity. The positive inotropic effect of CAP on the left auricle was concentration-dependent (0.03-6.5 microM). The positive inotropic effect of 0.33 microM CAP was reproducible at intervals of 15 min, whereas tachyphylaxis developed at shorter intervals or higher concentrations of CAP. The percent increase in the size of contractions by 0.33 microM CAP was smaller when [Ca2+]e was doubled but larger when 2.2 microM verapamil or 0.1 mM La3+ was present. The increase in contractions by 0.4-400 microM isoproterenol was greatly reduced by 0.33 microM CAP in a noncompetitive manner. The positive inotropic effect of 2.9 microM glucagon was also inhibited by 0.33 microM CAP. In the isolated anoestrous rat uterus 0.03-3.3 microM CAP caused a transient inhibition of the spontaneous contractions similarly to the effect of 2.2 microM verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D005934:Glucagon / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014590:Uterine Contraction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D007811:Lanthanum; D005934:Glucagon; D014700:Verapamil; D007545:Isoproterenol; D002211:Capsaicin; D002118:Calcium