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 rat isolated seminal vesicle, with an EC50 of 7.2 nM and an Emax of 0.24 +/- 0.03 g/100 mg wet tissue. In contrast, norepinephrine (NE) and acetylcholine (ACh) caused short-lasting phasic contractions, yielding EC50s of 8.0 and 30.3 microM and Emaxs of 1.99 +/- 0.21 and 2.16 +/- 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 ETA 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 microM) or ACh (10 microM). Indomethacin (5.6 microM) reduced ET-1-induced contractions and abolished the potentiation of responses to ATP. Big ET-1 also contracted the preparation, being 10- to 15-fold less potent than ET-1. Therefore ET-1 causes modest tonic contractions of the rat seminal vesicle via stimulation of ETA receptors and selectively potentiates motor responses to ATP. Eicosanoids of the cycloxygenase pathway are involved in both effects.