Fenspiride inhibits histamine-induced responses in a lung epithelial cell line.
Using the human lung epithelial WI26VA4 cell line, we investigated the capacity of fenspiride, an anti-inflammatory drug with anti-bronchoconstrictor properties, to interfere with histamine-induced intracellular Ca2+ increase and eicosanoid formation. Histamine and a histamine H1 receptor agonist elicited a rapid and transient intracellular Ca2+ increase (0-60 s) in fluo 3-loaded WI26VA4 cells. This response was antagonized by the histamine H1 receptor antagonist, diphenhydramine, the histamine H2 receptor antagonist, cimetidine, having no effect. Fenspiride (10(-7)-10(-5) M) inhibited the histamine H1 receptor-induced Ca2+ increase. In addition, histamine induced a biphasic increase in arachidonic acid release. The initial rise (0-30 s), a rapid and transient arachidonic acid release, was responsible for the histamine-induced intracellular Ca2+ increase. In the second phase release (15-60 min), a sustained arachidonic acid release appeared to be associated with the formation of cyclooxygenase and lipoxygenase metabolites. Fenspiride (10(-5) M) abolished both phases of histamine-induced arachidonic acid release. These results suggest that anti-inflammatory and antibronchoconstrictor properties of fenspiride may result from the inhibition of these effects of histamine.
Quartulli
F
F
Laboratoire Macrophages-Médiateurs de l'Inflammation et Interactions Cellulaires, UPS EA 2405, INSERM Institut Fédératif de Recherche 31 Louis Bugnard, CHU Rangueil, Toulouse, France.
Pinelli
E
E
Broué-Chabbert
A
A
Gossart
S
S
Girard
V
V
Pipy
B
B
D016718:Arachidonic Acid / Q000378:metabolism; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002927:Cimetidine / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004155:Diphenhydramine / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D016859:Lipoxygenase Inhibitors; D008168:Lung / Q000187:drug effects*; D013141:Spiro Compounds / Q000494:pharmacology*
D001993:Bronchodilator Agents; D016861:Cyclooxygenase Inhibitors; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D016859:Lipoxygenase Inhibitors; D013141:Spiro Compounds; D016718:Arachidonic Acid; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine; C084775:fenspiride; D002118:Calcium