Different mechanisms involved in relaxation of guinea-pig trachea by endothelin-1 and -3.
The effects of endothelin-1 and endothelin-3 were investigated on carbachol-contracted guinea-pig isolated trachea. Endothelin-1 and endothelin-3 (0.1-100 nM) induced partial dose-dependent relaxation of the precontracted preparations. The endothelin-1-induced relaxation was markedly attenuated by haemoglobin (10 microM) and methylene blue (10 microM) and by epithelium removal. In contrast, endothelin-3-induced relaxation was not affected by haemoglobin, methylene blue or epithelium removal. The large conductance Ca(2+)-activated K(+)-channel blocker, charybdotoxin, antagonized the endothelin-1- and the endothelin-3-induced relaxation to the same extent. These results show that both endothelin-1 and endothelin-3 relaxant activities are modulated by charybdotoxin-sensitive K(+)-channels, while the nitric oxide pathway is only involved in endothelin-1 relaxant effects.
Hadj-Kaddour
K
K
Laboratoire de Pharmacodynamie, Faculté de Pharmacie, Montpellier, France.
Michel
A
A
Chevillard
C
C
D000818:Animals; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D019334:Endothelin-3 / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D014132:Trachea / Q000187:drug effects*
D019332:Endothelin-1; D019334:Endothelin-3