Leukotriene D4 elicits a non-sustained contraction of the guinea pig trachea in calcium-free buffer.
The contraction of the isolated guinea pig trachea elicited by leukotriene D4 (LTD4) in Ca2+-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 LTD4. In contrast, LTD4 elicited a sustained contraction in the presence of 1.8 mM calcium. This sustained contraction in the presence of calcium was reproduced upon repeated LTD4 challenge, whereas in Ca2+-free buffer, only one LTD4-induced contraction could be obtained. The amplitude of the LTD4-induced contraction in Ca2+-free buffer decreased in a time-dependent manner which was also dependent upon the concentration of LTD4. At 10(-7) and 10(-6) M LTD4, small contractions (11% and 20% of control, respectively) were measured after 30 min in Ca2+-free buffer, whereas 10(-8) M LTD4 elicited a contraction at 15 min but not after 30 min in Ca2+-free buffer. Whereas washing the trachea for 5 min with LaCl3 (1.8 mM) only partially suppressed the LTD4-induced contraction in the presence of calcium, the contraction elicited by LTD4 in Ca2+-free buffer was not affected by LaCl3. The LTD4-induced contraction in Ca2+-free buffer was not affected by verapamil (10(-6) M); in contrast, the putative intracellular calcium antagonist, TMB-8 (10(-4) M), blocked the LTD4-induced contraction. These results provide evidence that the release of an intracellular calcium store plays an important role in the initiation of the LTD4-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 LTD4-induced contraction.
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004533:Egtazic Acid / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / 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*; D013997:Time Factors; D014132:Trachea / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D013189:SRS-A; D004533:Egtazic Acid; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D011189:Potassium Chloride; D007811:Lanthanum; D014700:Verapamil; D002118:Calcium