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 mediator which is generated in the cornea after injury. Its activity is regulated by interaction with specific receptors. The binding of PAF to its receptors initiates biochemical sequences that cluminate in the release of additional lipid mediators. An arachidonoyl-dependent phospholipase A2 is activated to release arachidonic acid from membrane phospholipids, especially phosphatidylcholine and ethanolamine. Arachidonic acid is then predominantly metabolized by the cyclooxygenase pathway to prostaglandins F2 alpha, E2 and D2, whereas the lipoxygenase pathway is not influenced by PAF. The release of arachidonic acid and prostaglandins stimulated by PAF is challenged by the PAF receptor antagonists BN 50727 and BN 50730. PAF acting intracellularly may also induce 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 beneficial in the management of ocular inflammatory disease.
Hurst
J S
JS
Louisiana State University Medical Center School of Medicine, LSU Eye Center, New Orleans, USA.
Bazan
H E
HE
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001381:Azepines / Q000494:pharmacology*; D003315:Cornea / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D010740:Phospholipases / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011817:Rabbits; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D058924:Thienopyridines; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D058924:Thienopyridines; D014230:Triazoles; C039351:platelet activating factor receptor; C066686:BN 50730; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D010740:Phospholipases; C067429:Setipafant