Leukotriene D4 elicits a non-sustained contraction of the guinea pig trachea in calcium-free buffer

Abstract The contraction of the isolated guinea pig trachea elicited by leukotriene D 4 (LTD 4 ) in Ca 2+ -free buffer (containing 10 −4 M EGTA) achieved a maximum at 6–8 min and relaxed back to baseline approximately 25 min after challenge with LTD 4 . In contrast, LTD 4 elicited a sustained contraction in the presence of 1.8 mM calcium. This sustained contraction in the presence of calcium was reproduced upon repeated LTD 4 challenge, whereas in Ca 2+ -free buffer, only one LTD 4 -induced contraction could be obtained. The amplitude of the LTD 4 -induced contraction in Ca 2+ -free buffer decreased in a time-dependent manner which was also dependent upon the concentration of LTD 4 . At 10 −7 and 10 −6 M LTD 4 , small contractions (11% and 20% of control, respectively) were measured after 30 min in Ca 2+ -free buffer, whereas 10 −8 M LTD 4 elicited a contraction at 15 min but not after 30 min in Ca 2+ -free buffer. Whereas washing the trachea for 5 min with LaCl 3 (1.8 mM) only partially suppressed the LTD 4 -induced contraction in the presence of calcium, the contraction elicited by LTD 4 in Ca 2+ -free buffer was not affected by LaCl 3 . The LTD 4 -induced contraction in Ca 2+ -free buffer was not affected by verapamil (10 −6 M); in contrast, the putative intracellular calcium antagonist, TMB-8 (10 −4 M), blocked the LTD 4 -induced contraction. These results provide evidence that the release of an intracellular calcium store plays an important role in the initiation of the LTD 4 -induced contraction of the guinea pig trachea. In addition, these results suggest that an extracellular calcium source may account for a small part of the LTD 4 -induced contraction.