Functional characterization of endothelin receptors in the bovine retractor penis muscle and penile artery

Pharmacol Toxicol. 1996 Aug;79(2):73-9. doi: 10.1111/j.1600-0773.1996.tb00245.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cattle
  • Dose-Response Relationship, Drug
  • Endothelin Receptor Antagonists*
  • Endothelin-1 / pharmacology*
  • Endothelins / pharmacology
  • Enzyme Activation / drug effects
  • Lethal Dose 50
  • Male
  • Muscle Relaxation / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Nitric Oxide Synthase / metabolism
  • Penis / blood supply
  • Penis / drug effects*
  • Peptide Fragments / pharmacology
  • Peptides, Cyclic / pharmacology
  • Vasoconstrictor Agents / toxicity*
  • Viper Venoms / toxicity*

Substances

  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Endothelins
  • Peptide Fragments
  • Peptides, Cyclic
  • Vasoconstrictor Agents
  • Viper Venoms
  • sarafotoxins s6
  • Cys(11)-Cys(15)-endothelin-1 (11-21)
  • Nitric Oxide Synthase
  • cyclo(Trp-Asp-Pro-Val-Leu)