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 microM), tetrodotoxin (1 microM) or guanethidine (10 microM). The rank order of potency of the endothelin isopeptides was endothelin-1>endothelin-2> or =endothelin-3. Sarafotoxin S6B was approximately equipotent with endothelin-1 in eliciting tonic contractions, but neither of the selective endothelin ET(B) receptor-agonists, sarafotoxin S6C (0.1 nM-0.3 microM) and BQ3020 (Ac-[Ala (11,15)]endothelin-1(6-21); 0.1 nM-0.3 microM), affected prostatic smooth muscle tone. The selective endothelin ET(A) receptor antagonist, BQ123 (cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp; 1 microM), attenuated responses to endothelin-1, -2 and -3, while the non-selective endothelin receptor antagonist bosentan (1 microM) and the selective endothelin ET(B) receptor antagonist BQ788, (Dmpc-gamma-MeLeu(9)-D-Trp(l-CO(2)CH(3))-D-Nle-OH; 1 microM) attenuated responses to endothelin-3 only. Contractions induced by exogenous administration of noradrenaline were unaffected by preincubation of tissues in BQ123 (1 microM) indicating the selectivity of this antagonist. These data suggest that endothelins mediate contractions of the rat prostate by action at endothelin ET(A) receptors.
Salamoussa
A
A
Department of Pharmacology, Monash University, PO Box 13E, 3800, Victoria, Australia.
Lau
W A
WA
Pennefather
J N
JN
Ventura
S
S
D000818:Animals; D000077300:Bosentan; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D019333:Endothelin-2 / Q000494:pharmacology; D019334:Endothelin-3 / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013449:Sulfonamides / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D019333:Endothelin-2; D019334:Endothelin-3; D016232:Endothelins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C086539:BQ 788; D000077300:Bosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)