Effect of SCH 37224 on anti-IgE-induced formation of sulfidopeptide leukotrienes in human lung parenchyma.
SCH 37224, 1-(1,2-dihydro-4-hydroxy-2-oxo-1-phenyl-1,8-naphthyridin-3-yl) pyrrolidinium, is a structurally novel compound that had been shown to inhibit leukotriene D4 formation in guinea pig lung in vitro. We tested whether SCH 37224 is able to inhibit both the formation of eicosanoids from human lung parenchyma in vitro and the binding of sulfidopeptide leukotrienes to membranes of lung parenchyma and bronchi. SCH 37224, at a concentration of 30 and 100 microM, was able to inhibit antigen-induced formation of sulfidopeptide leukotrienes, measured as leukotriene E4, while it did not significantly affect the formation of prostaglandin D2. At concentrations up to 100 microM, it did not affect either the binding of [3H]leukotriene C4 to membranes of human lung parenchyma or human bronchi, or the binding of [3H]leukotriene D4 to the parenchyma. In conclusion, SCH 37224 is a selective inhibitor of leukotriene formation in human lung in vitro, which might be of potential therapeutic interest in the treatment of asthma.
Viganò
T
T
Institute of Pharmacological Sciences, Milan, Italy.
Crivellari
M T
MT
Accomazzo
M R
MR
Monopoli
A
A
Belloni
P A
PA
Torre
M
M
Nicosia
S
S
Folco
G C
GC
D015777:Eicosanoids / Q000096:biosynthesis; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000096:biosynthesis*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D009287:Naphthyridines / Q000494:pharmacology*; D013189:SRS-A / Q000378:metabolism
D015777:Eicosanoids; D015289:Leukotrienes; D009287:Naphthyridines; D013189:SRS-A; C058078:Sch 37224; D007073:Immunoglobulin E