Pharmacological profiles of contractile endothelin receptors in guinea pig hilar bronchus.
Characterization of the receptors mediating contractions to endothelin-1 (ET-1), endothelin-3 (ET-3), sarafotoxin S6c (STXc), or IRL 1620 in isolated epithelium-denuded hilar bronchus of guinea pig using as antagonists BQ-123 (ETA receptor-selective) and Ro 46-2005 (ETA/B nonselective) was investigated. ET-1, ET-3, STXc, and IRL 1620 produced only contraction, and their concentration-response curves were obtained at the same concentration range (10(-10)-10(-7) M). The potency order was the following: STXc = ET-3 = ET-1 > IRL 1620. BQ-123 (10(-5)M) had no marked effect on the contraction induced by ET-3 or STXc, whereas it attenuated the response induced by high concentration of ET-1 (3 x 10(-8)-10(-7)M). The contraction induced by IRL 1620 was antagonized by BQ-123 (3 x 10(-6)-10(-5)M). Ro 46-2005 (10(-5)M) failed to inhibit the responses to ET-1 and ET-3. Ro 46-2005 (10(-5)M) slightly, but significantly, shifted the concentration-response curve for STXc to the right (pKB = 4.94 +/- 0.10, n = 7), and the maximum response was potentiated to about 127%. The curve for IRL 1620 was shifted in parallel by Ro 46-2005 (3 x 10(-6)-10(-5)M) to the right (mean pKB = 6.35 +/- 0.09, n = 8). These results suggest that ETB receptors primarily mediate contraction to ET-1, ET-3, STXc, and IRL 1620, and the relative inhibitory activities of ET antagonists vary with the agonist used. However, ET-1 and ET-3 might also activate non-ETB receptor or unknown mechanisms.
Kizawa
Y
Y
Department of Physiology and Anatomy, Nihon University College of Pharmacy, Chiba, Japan.
Nakajima
Y
Y
Nakano
J
J
Uno
H
H
Sano
M
M
Murakami
H
H
D000818:Animals; D001667:Binding, Competitive; D001980:Bronchi / Q000378:metabolism*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology; D000096926:Benzenesulfonamides
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011743:Pyrimidines; D017466:Receptors, Endothelin; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C074308:sovateltide; C083751:Ro 46-2005; D000096926:Benzenesulfonamides; C072247:cyclo(Trp-Asp-Pro-Val-Leu)