The contractile effects of endothelins on the smooth muscle of the rat prostate gland

Endothelin-1 elicited tonic contractions of rat prostatic smooth muscle that were unaffected by prazosin (0.5 mu M), tetrodotoxin (1 mu M) or guanethidine (10 mu M). The rank order of potency of the endothelin isopeptides was endothelin-1 > endothelin-2 greater than or equal to endothelin-3. Sarafotoxin S6B was approximately equipotent with endothelin-1 in eliciting tonic contractions, but neither of the selective endothelin ETB receptor-agonists, sarafotoxin S6C (0.1 nM-0.3 mu M) and BQ3020 (Ac-[Ala(11,15)]endothelin-1(6-21); 0.1 nM-0.3 mu M), affected prostatic smooth muscle tone. The selective endothelin ETA receptor antagonist, BQ123 (cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp; 1 mu M), attenuated responses to endothelin-1, -2 and -3, while the non-selective endothelin receptor antagonist bosentan (1 mu M) and the selective endothelin ETB receptor antagonist BQ788, (Dmpc-gamma-MeLeu(9)-D-Trp(1-CO2CH3)-D-Nle-OH; 1 mu M) attenuated responses to endothelin-3 only. Contractions induced by exogenous administration of noradrenaline were unaffected by preincubation of tissues in BQ123 (1 mu M) indicating the selectivity of this antagonist. These data suggest that endothelins mediate contractions of the rat prostate by action at endothelin ETA receptors. (C) 2000 Elsevier Science B.V. All rights reserved.