F. Quartulli et al., FENSPIRIDE INHIBITS HISTAMINE-INDUCED RESPONSES IN A LUNG EPITHELIAL-CELL LINE, European journal of pharmacology, 348(2-3), 1998, pp. 297-304
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.