FENSPIRIDE INHIBITS HISTAMINE-INDUCED RESPONSES IN A LUNG EPITHELIAL-CELL LINE

Using the human lung epithelial W126VA4 cell line, we investigated the capacity of fenspiride, an anti-inflammatory drug with anti-bronchoco nstrictor properties, to interfere with histamine-induced intracellula r Ca2+ increase and eicosanoid formation. Histamine and a histamine H- 1 receptor agonist elicited a rapid and transient intracellular Ca2+ i ncrease (0-60 s) in flue 3-loaded W126VA4 cells. This response was ant agonized by the histamine H-1, receptor antagonist, diphenhydramine, t he histamine H-2 receptor antagonist, cimetidine, having no effect. Fe nspiride (10(-7)-10(-5) M) inhibited the histamine H-1 receptor-induce d Ca2+ increase. In addition, histamine induced a biphasic increase in arachidonic acid release. The initial rise (0-30 s), a rapid and tran sient arachidonic acid release, was responsible for the histamine-indu ced intracellular Ca2+ increase. In the second phase release (15-60 mi n), a sustained arachidonic acid release appeared to be associated wit h the formation of cyclooxygenase and lipoxygenase metabolites. Fenspi ride (10(-5) M) abolished both phases of histamine-induced arachidonic acid release. These results suggest that anti-inflammatory and antibr onchoconstrictor properties of fenspiride may result from the inhibiti on of these effects of histamine. (C) 1998 Elsevier Science B.V. All r ights reserved.