Leukotriene D4 contractions in human airways are blocked by SK&F 96365, an inhibitor of receptor-mediated calcium entry
Gorenne, I.; Labat, C.; Gascard, J.P.; Norel, X.; Nashashibi, N.; Brink, C.
Journal of Pharmacology and Experimental Therapeutics 284(2): 549-552
1998
ISSN/ISBN: 0022-3565 PMID: 9454796 Document Number: 495710
In human bronchial muscle preparations, nifedipine (3 muM) significantly inhibited the histamine, ACh and KCl contractions. However, the dihydropyridine did not modify the contractile responses induced by either leukotriene D4 (LTD4) or antihuman IgE (a-IgE). In human airways, SK&F 96365 (30 muM and 100 muM) markedly reduced the KCl and, at the higher concentration, LTD4 maximal contractions. In addition, when preparations were treated with nifedipine (3 muM), SK and F 96365 (100 muM) significantly blocked responses to both LTD4 and a-IgE. The calcium chelating agent ethylene glycol-bis (beta-amino-ethyl ether) N,N,N',N'-tetraacetic acid (4 mM) also inhibited the aIgE-induced contractions. These data demonstrate that the nifedipine-resistant component of the LTD4 and a-IgE contractions was inhibited by SK&F 96365 and suggest that the cysteinyl-leukotriene receptor in human airways may be intimately linked with a receptor-operated calcium-entry mechanism.