Lack of effect of leukotriene D4 on Ca-uptake in airway smooth muscle.
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.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005480:Flurbiprofen / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D013189:SRS-A / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D013189:SRS-A; D005480:Flurbiprofen; D011189:Potassium Chloride; D007811:Lanthanum; D014700:Verapamil; D002118:Calcium