LEUKOTRIENE D-4 CONTRACTIONS IN HUMAN AIRWAYS ARE BLOCKED BY SK-AND-F96365, AN INHIBITOR OF RECEPTOR-MEDIATED CALCIUM-ENTRY

In human bronchial muscle preparations, nifedipine (3 mu M) significan tly inhibited the histamine, ACh and KCl contractions. However, the di hydropyridine did not modify the contractile responses induced by eith er leukotriene D-4 (LTD4) or anti-human IgE (a-IgE). In human airways, SK&F 96365 (30 mu M and 100 mu M) markedly reduced the KCl and, at th e higher concentration, LTD4 maximal contractions. In addition, when p reparations were treated with nifedipine (3 mu M), SK&F 96365 (100 mu M) 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 a-IgE-induced contraction s. These data demonstrate that the nifedipine-resistant component of t he LTD4 and a-IgE contractions was inhibited by SK&F 96365 and suggest that the cysteinyl-leukotriene receptor in human airways may be intim ately linked with a receptor-operated calcium-entry mechanism.