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

Abstract

In the guinea-pig terminal ileum a maximally effective concentration of prostacyclin (PGI2) (1 mumol/l) induced contractions that were partially resistant to tetrodotoxin (TTX) 0.1 mumol/l, to low temperature (20 degrees 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 mumol/l) caused a concentration-dependent inhibition of contractions induced by PGI2 (20 nmol/l and 1 mumol/l) and by equieffective concentrations of ACh (20 nmol/l and 0.4 mumol/l, respectively). The order of magnitude for this inhibition was ACh 20 nmol/l = PGI2 20 nmol/l greater than PGI2(1) mumol/l greater than ACh 0.4 mumol/l. In preparations exposed to TTX or to low temperature procaine (50 mumol/l) did not affect the residual response to PGI2 (1 mumol/l). Quercetin (1 and 5 mumol/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 mumol/l. Carbonyl cyanide-trifluoro-methoxyphenyl hydrazone (FCCP) (0.1-1 mumol/l) reduced the effect of PGI2 and of ACh to approximately the same extent and inhibited the residual response to PGI2 1 mumol/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.