EFFECT OF CALCIUM-ANTAGONISTS ON LEUKOTRIENE-D-4-INDUCED CONTRACTIONS OF THE GUINEA-PIG TRACHEA AND LUNG PARENCHYMA

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 225  (2) , 310-315
Abstract
The directly mediated contractile activity of leukotriene (LT) D4 on isolated guinea pig trachea and lung parenchyma was dependent upon the presence of Ca in the bathing buffer. Whereas 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8), a Ca antagonist believed to act intracellularly, completely antagonized the LTD4-induced contraction, the Ca channel entry blockers, nifedipine and verapamil, only partially inhibited LTD4 contractile activity; diltiazem was inactive. TMB-8, nifedipine and verapamil were more effective in blocking the contraction of the trachea elicited by KCl-induced membrane depolarization than the contraction induced by LTD4. Of the channel entry blockers, only nifedipine appeared capable of partially relaxing an established LTD4-contracted trachea, whereas TMB-8 almost completely reversed the LTD4 contraction. On the lung parenchyma, the LTD4-induced contraction was suppressed, but not abolished in Ca2+-free buffer; this contraction was antagonized by meclofenamic acid, thus suggesting it could be due in part to the indirect thromboxane (Tx)A2-mediated pathway of LT action. In Ca2+-free buffer, LTD4 was sill capable of generating TxB2 [thromboxane B-2], although lower amounts were found when compared to Ca2+-containing buffer. Incremental addition of Ca to the parenchyma in Ca2+-free buffer containing LTD4 elicited greater than control LTD4-induced contraction and TxB2 generation. Neither the contraction of the parenchyma nor the generation of TxB2 was antagonized by nifedipine; conversely, TMB-8 blocked both completely. Based upon the use of pharmacological antagonists of Ca, LTD4 contractile activity in the respiratory system apparently is dependent on Ca, with Ca of intracellular origin potentially of significant.