Effects of leukotriene D4 and antagonists of arachidonic acid metabolism and calcium entry on guinea pig tracheal muscle responsiveness.
We studied the effects of antagonists of arachidonic acid metabolism and calcium entry on the responsiveness of airway smooth muscle to acetylcholine (ACh), potassium and norepinephrine. Responsiveness in vitro was assessed by measuring isometric contraction of guinea pig trachealis muscle upon chemical stimulation. We found that indomethacin potentiated the response of airway muscle to ACh and KCl, but not to norepinephrine. The indomethacin-induced potentiation observed was inhibited by both BW 755C and nifedipine. As occurred with indomethacin pretreatment, we also found that a noncontractile concentration of leukotriene D4 (LTD4) potentiated the responsiveness of tracheal muscle to both ACh and KCl. Our data suggest that indomethacin- and LTD4-potentiation of guinea pig airway muscle responsiveness to certain bronchoconstrictors may be mediated, at least in part, by enhanced extracellular Ca++ entry.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D013189:SRS-A / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D011720:Pyrazoles; D013189:SRS-A; D016718:Arachidonic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D011189:Potassium Chloride; D009543:Nifedipine; D000109:Acetylcholine; D007213:Indomethacin