8-Iso-prostaglandin F-2 alpha release from isolated and perfused guinea-pig
lung was measured by radioimmunoassay. 8-Iso-prostaglandin F-2 alpha relea
se was detectable under basal conditions and increased 10-fold during antig
en-induced bronchoconstriction, concomitant with the increase of thromboxan
e B-2 and prostaglandin E-2. The anti-8-iso-prostaglandin F-2 alpha serum u
sed in the radioimmunoassay seems to be quite specific for this compound. P
retreatment of lungs with indomethacin (a non-selective inhibitor of cycloo
xygenase) reduced 8-iso-prostaglandin F-2 alpha release under basal conditi
ons and completely abolished the increase observed during lung anaphylaxis.
Pretreatment of lungs with NS 398 (N-[2-cyclohexyl]-4-nitrophenyl methanes
ulphonamide), a selective inhibitor of cyclooxygenase-2, did not change bas
al or antigen-induced 8-iso-prostaglandin F-2 alpha release at all. We conc
lude that under basal conditions guinea-pig lung perfusates contain low lev
els of 8-iso-prostaglandin F-2 alpha-like immunoreactivity, which increase
10-fold during antigen-induced bronchoconstriction. This isoprostane seems
to be derived from the cyclooxygenation of arachidonic acid via the constit
utive form of cyclooxygenase. (C) 1999 Elsevier Science B.V. All rights res
erved.