title: Study of mechanisms mediating contraction to leukotriene C4, D4 and other bronchoconstrictors on guinea pig trachea.
abstract: Contractions of guinea pig trachea in the absence and presence of indomethacin to LTD4 greater than LTC4 greater than K+ greater than histamine greater than acetylcholine were reduced following a 45 minute exposure of the tissues to calcium-free Krebs' solution (Ca2+-free Krebs' solution), were further reduced by a transient exposure to EGTA (1.25 mM) in Ca2+-free Krebs' solution and were virtually abolished when tested in the presence of EGTA (0.125 mM) in Ca2+-free Krebs' solution. In normal Krebs' solution (2.5 mM Ca2+) the Ca2+ entry blockers nifedipine (N) much greater than D-600 greater than verapamil (V) greater than diltiazem (D) almost completely abolished the contractions to K+ but blocked only a component of the maximum response to the other agonists. After exposure to Ca2+-free Krebs' solution for 45 minutes, any residual contractions to LTC4 & LTD4, were reversed by low concentrations of N (0.3 microM) or D-600 (2.1 microM). Leukotrienes appear to mobilize a superficial and a bound store of Ca2+ which gains entry through at least two types of Ca2+ channels (or mechanisms), one of which is blocked by N and D600. K+-induced contractions appear to be dependent on superficial and tightly bound Ca2+ but entry is solely through channels which are blocked by the Ca2+ entry blockers studied. Contraction to histamine and acetylcholine persisted following exposure of the tissues to Ca2+ free Krebs' solution but contractile activity was virtually abolished in Ca2+ free Krebs' solution containing EGTA. Residual contractions to histamine and part of the residual contractions to acetylcholine in Ca2+-free Krebs' solution were blocked by low dose N (0.3 microM) or D600 (2.1 microM). These findings suggest a major role for extracellular Ca2+ during spasmogen-induced contraction in this tissue.
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D013189:SRS-A / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D013189:SRS-A; D006632:Histamine; D000109:Acetylcholine; D007213:Indomethacin