ETB-type receptors mediate endothelin-stimulated contraction in the aortic vascular smooth muscle of the spiny dogfish shark, Squalus acanthias.
Using various agonists, and the specific antagonist BQ-123, we have examined the sensitivity to endothelin of the vascular smooth muscle of the ventral aorta of the spiny dogfish shark, Squalus acanthias. Human endothelin-1 produced significant contraction of isolated vascular smooth muscle rings, with an EC50 of 10 nmol.l-1. The presence of an intact endothelium did not alter this response but the magnitude of the contraction was greater in rings with an intact endothelium. The response to 0.2 mumol.l-1 endothelin-1 was equivalent to that of 0.1 mmol.l-1 acetylcholine, and significantly greater than that to 80 mmol.l-1 KCl, suggesting high sensitivity even to the heterologous, mammalian peptide. The Hill plot of the contractile response was a straight line with a slope of 1.12, indicating that a single receptor was mediating the response. Endothelin-1, endothelin-3, and sarafotoxin S6c produced similar concentration-response curves, and the response to endothelin-1 was insensitive to the ETA-specific inhibitor BQ-123. Our data are consistent with the hypothesis that the receptor involved in the contractile response to endothelin of shark aortic vascular smooth muscle is of the ETB-rather than the ETA-type.
Evans
D H
DH
Mt. Desert Island Biological Laboratory, Salsbury Cove, ME 04672, USA.
Gunderson
M
M
Cegelis
C
C
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D004284:Dogfish / Q000502:physiology*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000187:drug effects* / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C072247:cyclo(Trp-Asp-Pro-Val-Leu)