Functional characterization of endothelin receptors in the bovine retractor penis muscle and penile artery.
The effects of endothelin-1 and sarafotoxin 6c on the bovine retractor penis muscle and the bovine penile artery were studied, and a functional characterization of endothelin receptors in these tissues was performed by using the ETA-receptor antagonist BQ-123 and the ETB-receptor antagonist IRL 1038. The retractor penis muscle and the penile artery were about equipotently contracted by endothelin-1 in a concentration-dependent manner the EC50 values being 3.5 x 10(-9) M and 1.3 x 10(-9) M, respectively. In both tissues BQ-123 (10(-6) M) inhibited maximal contraction induced by endothelin-1 by about 50%. Sarafotoxin 6c substantially relaxed the retractor penis muscle, and to a lesser extent also the penile artery, whereas endothelin-1 did not relax either tissue. The sarafotoxin 6c-induced relaxation of the retractor penis muscle was totally inhibited by IRL 1038 (3 x 10(-6) M) and the nitric oxide synthase inhibitor L-NNA (10(-4) M). In both tissues L-NNA enhanced the contraction induced by endothelin-1 and lowered the threshold concentration for it. The results show that in both tissues the contraction induced by endothelin-1 was mediated primarily by ETA-receptors. The retractor penis muscle is also equipped with ETB-receptors, probably at least in part located on the inhibitory nerves, which mediate relaxation via activation of the L-arginine nitric oxide synthase pathway.
Parkkisenniemi
U M
UM
Department of Pharmacy, University of Helsinki, Finland.
Klinge
E
E
D000704:Analysis of Variance; D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010413:Penis / Q000098:blood supply / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000633:toxicity*; D014757:Viper Venoms / Q000633:toxicity*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C077420:Cys(11)-Cys(15)-endothelin-1 (11-21); D019001:Nitric Oxide Synthase; C072247:cyclo(Trp-Asp-Pro-Val-Leu)