Arachidonic acid metabolism and modulation of in vitro anaphylaxis by 5,8,11,14-eicosatetraynoic acid and 9a,12a-octadecadiynoic acid.

M Hitchcock, N A Kokolis

Index: Br. J. Pharmacol. 72(4) , 689-95, (1981)

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Abstract

1. 5,8,11,14-Eicosatetraynoic acid (ETYA) inhibited the antigen-induced contractions of tracheal spirals obtained from actively sensitized guinea-pigs. Consistent data were obtained only when the spirals were treated with indomethacin. 2. ETYA did not affect histamine-induced contractions of indomethacin-treated tracheal spirals. 3. 9a, 12a-Octadecadiynoic acid (Ro-3-1314) a potential inhibitor of linoleic acid metabolism, stimulated the antigen-induced contraction of guinea-pig tracheal spirals and the immunological release of slow reacting substances of anaphylaxis (SRS-A) from actively sensitized guinea-pig lung fragments. 4. Both ETYA and Ro-3-1314 inhibited the immunological release of malondialdehyde from guinea-pig lung fragments. 5. The data indicate that the effects of ETYA were due to inhibition of lipoxygenase and the effects of Ro-3-1314 were due to inhibition of cyclo-oxygenase. 6. The results suggest that products of lipoxygenase contribute to the antigen-induced contraction of guinea-pig lung, particularly when cyclo-oxygenase is inhibited. Under these conditions there may be redirection of the metabolism of arachidonic acid to favour production of constrictor products of lipoxygenase such as SRS-A.