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

Abstract

The effects of verapamil on leukotriene D4 (LTD4)- and KCl-induced contractions and 45Ca-uptake were examined in guinea-pig isolated tracheal smooth muscle. 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. Verapamil (1 mumol l-1) inhibited the tension responses induced by both LTD4 and KCl. 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. 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 mumol l-1). 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.