title: Pharmacologic modulation of endothelin-induced contraction in isolated rat tracheal segments.
abstract: Porcine endothelin was found to be the most potent of the tested bronchoconstrictor agents on isolated rat tracheal segments. The calculated EC50S were as follows: endothelin = 106 nM, 5-HT = 1.45 microM, acetylcholine = 6 microM, KCl = 26.3 mM, and CaCl2 = 0.4 mM. Rat trachea is insensitive to histamine, neurokinin-A, and LTC4/LTD4. PAF (5.1 +/- 2.2 microM) produced strong contractile responses (1076 + 91 mg). Verapamil (1 microM, 60 min) antagonized CaCl2 but did not influence endothelin-induced contractile responses. In Ca2(+)-free Krebs solution, endothelin-induced responses were inhibited significantly. Relatively high concentrations of nifedipine and cadmium chloride (10 microM) attenuated endothelin-induced contractile responses. Indomethacin (5 microM, 60 min) slightly enhanced the endothelin-induced concentration-effect curve. These data show that endothelin induces slowly developing and sustained stimulus-contraction coupling in rat tracheal smooth muscle cells mainly by utilizing receptor-operated Ca2+ channels which are resistant to verapamil.
authors.affiliation: Department of Pharmacology, Wallace Laboratories, Division of Carter-Wallace Inc., Cranbury, New Jersey 08512.
authors.forename: N
authors.initials: N
authors.lastname: Chand
authors.forename: W
authors.initials: W
authors.lastname: Diamantis
authors.forename: R D
authors.initials: RD
authors.lastname: Sofia
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014132:Trachea / Q000187:drug effects / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D016232:Endothelins; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium