Characterization of endothelin receptors in rat renal artery in vitro.
1. The aim of this study was to investigate the function and characteristics of endothelin receptors in rat main branch renal artery in vitro. 2. Endothelin(ET)-1 (mean EC50 = 9.8 nM) was approximately 12 fold more potent than ET-3 (mean EC50 = 120 nM) as a contractile agonist and produced a greater maximum response. In contrast, neither of the ETB receptor-selective agonists, alanine[1,3,11,15]ET-1 nor sarafotoxin S6c, (0.1 nM-1 microM), induced any contractile effect, or any relaxant effect in endothelium-intact preparations pre-contracted with the thromboxane A2 mimetic, U-46619. Sarafotoxin S6c (30 nM) also failed to induce any further contraction in tissues pre-contracted with an EC50 concentration of ET-1. 3. The ETA receptor-selective antagonist, BQ123, behaved as a weak and variable antagonist of the contractile effects of ET-1 (mean pA2 estimates in the range 5.8-6.3). In contrast, BQ123 antagonized ET-3 with a potency (mean pA2 = 7.6) consistent with its affinity for ETA receptors. Co-incubation of BQ123 (3 microM) with the putative ETB receptor-selective antagonist, IRL1038 (10 microM), produced no greater antagonism of ET-1 responses than was induced by BQ123 (3 microM) alone. 4. In conclusion, ETB receptors do not appear to be present in rat main branch renal artery. The contractile effects of ET-3 in this tissue seem to be mediated by ETA receptors. While ETA receptors partly mediate the contractile effects of ET-1, these data raise the possibility that a population of novel BQ123-insensitive endothelin receptors may also contribute to this response.
Clark
K L
KL
Pharmacology 2, Glaxo Research and Development Limited, Hertfordshire, U.K.
Pierre
L
L
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000409:Alanine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000819:agonists / Q000187:drug effects*; D012077:Renal Artery / Q000187:drug effects* / Q000378:metabolism; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011450:Prostaglandin Endoperoxides, Synthetic; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C077420:Cys(11)-Cys(15)-endothelin-1 (11-21); D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000409:Alanine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)