Target sites for the inhibition of prostacyclin effect in guinea-pig ileum

Summary In the guinea-pig terminal ileum a maximally effective concentration of prostacyclin (PGI₂) (1 ol/l) induced contractions that were partially resistant to tetrodotoxin (TTX) 0.1 mol/l, to low temperature (20°C) and to atropine (30 nmol/l). Half maximum contractions evoked by PGI₂ (20 nmol/l) were abolished by TTX and by low temperature, which did not modify the response to exogenous acetylcholine (ACh), as well as by atropine. Procaine (5–500 ol/l) caused a concentration-dependent inhibition of contractions induced by PGI₂ (20 nmol/l and 1 mol/l) and by equieffective concentrations of ACh (20 nmol/l and 0.4 ol/l, respectively). The order of magnitude for this inhibition was ACh 20 nmol/l = PGI₂ 20 nmol/l > PGI₂1 mol/l > ACh 0.4 mol/l. In preparations exposed to TTX or to low temperature procaine (50 mol/l) did not affect the residual response to PGI₂ (1 mol/l). Quercetin (1 and 5 ol/l) inhibited the effect of PGI₂ and, at higher concentrations, it also caused partial depression of the responses to ACh. Quercetin did not alter TTX-resistant and low temperature-resistant contractions induced by PGI₂ 1 mol/l. Carbonyl cyanide-trifluoromethoxyphenyl hydrazone (FCCP) (0.1–1 ol/l) reduced the effect of PGI₂ and of ACh to approximately the same extent and inhibited the residual response to PGI₂ 1 mol/l in preparations treated with TTX or expressed to low temperature. The present results show that PGI₂, besides acting on cholinergic neurons, also exerts a direct effect on smooth muscle cells and FCCP can be used to block this effect. In contrast procaine and quercetin selectively inhibit the ACh-mediated component of PGI₂ action. Send offprint requests to R. M. Gaion