Lack of effect of leukotriene D4 on Ca‐uptake in airway smooth muscle

Abstract

1 The effects of verapamil on leukotriene D₄ (LTD₄)- and KCl-induced contractions and ⁴⁵Ca-uptake were examined in guinea-pig isolated tracheal smooth muscle. 2 Both LTD₄ (0.1 to 200 nmol l⁻¹) and KCl (8 to 125 mmol l⁻¹) produced concentration-dependent increases in tension in the tracheal preparations. 3 Verapamil (1 μmol l⁻¹) inhibited the tension responses induced by both LTD₄ and KCl. 4 LTD₄ failed to increase the lanthanum-resistant Ca content of tracheal smooth muscle at either low (EC₂₅; 3 nmol l⁻¹) or high (EC₉₀; 50 nmol l⁻¹) concentrations. Verapamil did not modify this result. 5 KCl (90 mmol l⁻¹) increased the lanthanum-resistant Ca content of the smooth muscle by approximately 60% over basal levels. This effect was completely inhibited by verapamil (1 μmol l¹). 6 It is concluded that in this tissue, LTD₄ utilizes principally an intracellular source of Ca²⁺ to initiate contraction whereas KCl is dependent upon the uptake of Ca²⁺ from the extracellular compartment. It is suggested that the inhibitory effects of verapamil may reflect an intracellular mechanism of action directed against Ca²⁺ release initiated by LTD₄.