Anaphylaxis increases 8-iso-prostaglandin F2alpha release from guinea-pig lung in vitro.
8-Iso-prostaglandin F2alpha, release from isolated and perfused guinea-pig lung was measured by radioimmunoassay. 8-Iso-prostaglandin F2alpha release was detectable under basal conditions and increased 10-fold during antigen-induced bronchoconstriction, concomitant with the increase of thromboxane B2 and prostaglandin E2. The anti-8-iso-prostaglandin F2alpha serum used in the radioimmunoassay seems to be quite specific for this compound. Pretreatment of lungs with indomethacin (a non-selective inhibitor of cyclooxygenase) reduced 8-iso-prostaglandin F2alpha release under basal conditions and completely abolished the increase observed during lung anaphylaxis. Pretreatment of lungs with NS 398 (N-[2-cyclohexyl]-4-nitrophenyl methanesulphonamide), a selective inhibitor of cyclooxygenase-2, did not change basal or antigen-induced 8-iso-prostaglandin F2alpha release at all. We conclude that under basal conditions guinea-pig lung perfusates contain low levels of 8-iso-prostaglandin F2alpha-like immunoreactivity, which increase 10-fold during antigen-induced bronchoconstriction. This isoprostane seems to be derived from the cyclooxygenation of arachidonic acid via the constitutive form of cyclooxygenase.
Montuschi
P
P
Institute of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy. p.montuschi@ic.uc.uk
Currò
D
D
Ragazzoni
E
E
Preziosi
P
P
Ciabattoni
G
G
D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D028441:F2-Isoprostanes; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D010047:Ovalbumin / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism