The effect of ethacrynic acid on the guinea-pig and rat isolated vas deferens.

1 The effect of ethacrynic acid (EA) was studied on guinea-pig and rat vas deferens in vitro.2 EA contracted the guinea-pig but not the rat vas deferens in a dose-dependent manner (50-800 mug/ml). Tyramine caused contraction in 10 out of 18 guinea-pig vas deferens; EA caused contraction in 17 of the preparations which did not respond to tyramine. Repeated doses of EA produced tachyphylaxis, but there was no cross tachyphylaxis to tyramine.3 The contractions produced by EA were prevented by phentolamine or reserpine pretreatment and potentiated by cocaine. A low concentration of desipramine (3 ng/ml) potentiated and higher concentrations (0.6 and 3.0 mug/ml) inhibited the response of vas deferens to EA.4 Hexamethonium (100 mug/ml) or atropine (0.1 mug/ml) did not inhibit the effect of EA, excluding the nicotinic and muscarinic receptors as the sites of action.5 The effect of noradrenaline (NA) on the guinea-pig and rat vas deferens was enhanced by EA pretreatment, which may be due to inhibition of NA uptake.6 It is concluded that EA releases NA from guinea-pig vas deferens. The mechanism of release seems to be different from that of tyramine.