A study of the mode and site of action of capsaicin in guinea-pig heart and rat uterus

Summary

• 1. 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.

• 2. 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.

• 3. The positive inotropic effect of CAP on the left auricle was concentration-dependent (0.03–6.5 μM). The positive inotropic effect of 0.33 μM 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 μM CAP was smaller when [Ca²⁺]_e was double but larger when 2.2 μM verapamil or 0.1 mM La³⁺ was present. The increase in contractions by 0.4–400 μM isoproterenol was greatly reduced by 0.33 μM CAP in a noncompetitive manner. The positive inotropic effect of 2.9 μM glucagon was also inhibited by 0.33 μM CAP.

• 4. In the isolated anoestrous rat uterus 0.03–3.3 μM CAP caused a transient inhibition of the spontaneous contractions similarly to the effect of 2.2 μM verapamil.

• 5. It is concluded that the positive inotropic effect of CAP in the left auricle may be due to an increase in [Ca²⁺]_i which does not result from a transmembraneous influx of Ca²⁺ but probably from a release of Ca²⁺ from stores inaccessible to either verapamil and La³⁺. The negative inotropic effect of CAP and the inhibition of the positive inotropic effects of isoproterenol and glucagon may be explained by an unspecific membrane-stabilizing effect of CAP. A membrane-stabilizing effect may also be responsible for the CAP-induced inhibition of the spontaneous contractions of the rat uterus.