Role of calcium in arachidonic acid-induced contractions of guinea pig airways.
We have previously shown that arachidonic acid (AA)-induced contractions of indomethacin-pretreated guinea pig trachea and parenchyma are due to the synthesis of leukotrienes C4 and D4. The present experiments were designed to investigate the role of calcium (Ca2+) in the above. AA (66 microM)-induced contractions of trachea, but not parenchyma, were reduced in Ca2+-free Krebs-Henseleit solution ( KHS ). However the contractions of both trachea and parenchyma were abolished in Ca2+-free KHS with either lanthanum chloride (1 mM) or EDTA (300 microM). The Ca2+ antagonists, verapamil (100 microM), nitrendipine (100 microM), and TMB-8 (100 microM), reduced AA-induced contractions of both trachea and parenchyma. Re-addition of Ca2+ (2.2 mM) to trachea and parenchyma in Ca2+-free KHS in the presence of lanthanum restored the AA-induced contractions. This effect of Ca2+ was reduced by verapamil (100 microM) or nitrendipine (100 microM). LTC4-induced contractions of trachea and parenchyma were unaffected by nitrendipine (100 microM), whereas tracheal contractions were reduced in Ca2+-free KHS . Both tracheal and parenchymal contractions to LTC4 were reduced in Ca2+-free KHS in the presence of lanthanum chloride (1 mM). We conclude that superficially bound pools of Ca2+ are important in AA-induced contractions of the airways. Furthermore, nitrendipine reduces AA-induced contractions by inhibiting AA metabolism and not by inhibiting airway smooth muscle contraction induced by released leukotrienes.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004492:Edetic Acid / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D008168:Lung; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009568:Nitrendipine; D013189:SRS-A / Q000494:pharmacology / Q000502:physiology*; D014132:Trachea; D014700:Verapamil / Q000494:pharmacology
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D013189:SRS-A; D016718:Arachidonic Acid; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D007811:Lanthanum; D009568:Nitrendipine; D004492:Edetic Acid; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium; D007213:Indomethacin