Leukotriene effect in airways smooth muscle: calcium dependency and verapamil inhibition.
The extracellular calcium (Ca++) E dependency of the synthetic leukotrienes (LT) C4, D4 and E4 and inhibition of LTC4 by verapamil was demonstrated on guinea pig trachealis in vitro. LTC4 exhibited an intrinsic potency 170 X greater than histamine. Tension development by LTC4, D4 and E4 was equipotent at 2.5 mM (Ca++)E. Tension studies in 0.5 mM (Ca++)E indicate these three leukotrienes to be (Ca++)E dependent with a potency ranking of LTC4 greater than LTD4 and LTE4 (P less than 0.05 and P less than 0.001 respectively). Inhibition of LTC4 by verapamil yielded an IC50 of approximately 1.1 X 10(-4)M with complete inhibition at 2.2 X 10(-4)M; this antagonism was non-competitive. The specific dependency of verapamil inhibition of LTC4 to (Ca++)E was demonstrated by reversal of verapamil antagonism with 5.0 mM (Ca++)E. Synthetic leukotrienes C4, D4 and E4 are dependent upon (Ca++)E for their myotropic activity, an action non-competitively inhibited by the calcium channel blocker verapamil.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D017999:Leukotriene E4; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D013189:SRS-A / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D013189:SRS-A; D017999:Leukotriene E4; D006632:Histamine; D014700:Verapamil; D000109:Acetylcholine; D002118:Calcium