ENDOTHELIN-1 CONTRACTS AND INCREASES MOTOR-RESPONSES TO ATP IN RAT SEMINAL-VESICLE

Endothelin-1 (ET-1; 0.3-100 nM) induced graded tonic contractions in r at isolated seminal vesicle, with an EC(50) of 7.2 nM and an E(max) of 0.24 +/- 0.03 g/100 mg wet tissue. In contrast, norepinephrine (NE) a nd ace tylcholine (ACh) caused short-lasting phasic contractions, yiel ding EC(50)s of 8.0 and 30.3 mu M and E(max)s of 1.99 +/- 0.21 and 2.1 6 +/- 0.31, respectively. ET-3 and sarafotoxin S6c were 10- to 30-fold less potent than ET-1. Contractions to ET-1 (1-100 nM) were markedly inhibited by the selective ET(A) receptor antagonist BQ-123 (300 nM). ET-1 also potentiated, in graded fashion, contractions induced by ATP (1 mM; 30 nM of ET-1 caused a 10-fold potentiation) but not by NE (3 m u M) or ACh (10 mu M) Indomethacin (5.6 mu M) reduced ET-1-induced con tractions and abolished the potentiation of responses to ATP. Big ET-1 also contracted the preparation, being 10- to 15-fold less potent tha n ET-1. Therefore ET-1 causes modest tonic contractions of the rat sem inal vesicle via stimulation of ET(A) receptors and selectively potent iates motor responses to ATP. Eicosanoids of the cycloxygenase pathway are involved in both effects.