ACTIVATION OF THE PHOSPHOLIPASE CYCLOOXYGENASE CASCADE IN THE RABBIT CORNEA BY PLATELET-ACTIVATING-FACTOR IS CHALLENGED BY PAF RECEPTOR ANTAGONISTS

Platelet-activating factor (PAF) is a potent lipid inflammatory mediat or which is generated in the cornea after injury. Its activity is regu lated by interaction with specific receptors. The binding of PAF to it s receptors initiates biochemical sequences that cluminate in the rele ase of additional lipid mediators. An arachidonoyl-dependent phospholi pase A(2) is activated to release arachidonic acid from membrane phosp holipids, especially phosphatidylcholine and ethanolamine. Arachidonic acid is then predominantly metabolized by the cyclooxygenase pathway to prostagiandins F-2 alpha, E(2) and D-2, whereas the lipoxygenase pa thway is not influenced by PAF. The release of arachidonic acid and pr ostaglandins stimulated by PAF is challenged by the PAF receptor antag onists BN 50727 and BN 50730. PAF acting intracellularly may also indu ce the synthesis of cyclooxygenase, presumably the 'inducible' isoform PGHS2, which has been implicated in the inflammatory response. Thus, the therapeutic use of PAF receptor angatonists could be potentially b eneficial in the management of ocular inflammatory disease.