Differences between endothelin receptors mediating contraction of guinea-pig aorta and pig coronary artery.
Endothelin receptors mediating contraction were characterized and compared in rings from guinea-pig thoracic aorta and pig left circumflex coronary artery. In guinea-pig aorta, the following rank order of agonist potencies was found (mean EC50 value, nM): endothelin-1 (5.0) = endothelin-2 (5.5) > vasoactive intestinal contractor (VIC; 11.0) > sarafotoxin S6b (39.8) > [Ala3,11]endothelin-1 (121) > sarafotoxin S6a (> 150) > endothelin-3 (> 500). [Ala1,3,11,15] Endothelin-1, endothelin-(16-21), sarafotoxin S6c and sarafotoxin S6d were neither agonists nor antagonists at concentrations up to 1, 10, 3 and 1 microM, respectively. Cyclo-(D-Trp-D-Asp-Pro-D-Val-Leu) (BQ-123; 0.1-1 microM) behaved as a competitive antagonist of endothelin-1 (pA2 7.4 +/- 0.1, slope factor 0.91 +/- 0.17, n = 4). In pig coronary artery, all endothelins and sarafotoxins were agonists, except for endothelin-(16-21). Sarafotoxin S6c, [Lys4]sarafotoxin S6c, [Nle6]sarafotoxin S6c and [Ala1,3,11,15]endothelin-1 acted as partial agonists (Emax about 40% of that of endothelin-1). The rank order of agonist potencies was: sarafotoxin S6c (1.5) = [Lys4]sarafotoxin S6c (1.5) > [Nle6]sarafotoxin S6c (6.7) > or = sarafotoxin S6a (7.5) > or = endothelin-1 (12.6) > or = sarafotoxin S6b (14.8) > or = VIC (18.3) = endothelin-2 (19.3) > or = [Ala1,3,11,15]endothelin-1 (41.7) > or = [Ala3,11]endothelin-1 (55.2) > endothelin-3 (96.8) > sarafotoxin S6d (> 200). Endothelin-(16-21) was neither agonist nor antagonist at 10 microM. The concentration-response curves of endothelin-3 and sarafotoxin S6a were biphasic, consisting of a higher sensitivity (40-45% of the total effect) and a lower sensitivity component. BQ-123 (0.1-1 microM) did not alter the concentration-response curve of endothelin-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Schoeffter
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Sandoz Pharma Ltd., Basel, Switzerland.
Randriantsoa
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A
D000595:Amino Acid Sequence; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects*; D065128:Endothelin Receptor Antagonists; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C072247:cyclo(Trp-Asp-Pro-Val-Leu)