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.