Novel cytochrome P450-dependent arachidonic acid metabolites and their ocular effects.
Our studies, as reviewed here, clearly show that in the cornea, and possibly in other ocular tissues, arachidonic acid derivatives other than the classical PGs or the more recently discovered leukotrienes can be formed, and that at least some of the AA metabolites produced via the cytochrome P450 system have potent biological activities. In fact, two of these metabolites, 12(R)-HETE (compound C) and 12-hydroxyeicosatrienoic acid (compound D; Fig. 1), appear to be much more potent than classical PGs with respect to their effect on active ion transport systems, vasodilation, or the breakdown of the blood-aqueous barrier. The fact that 12(R)-HETE was found to be a potent inhibitor of Na+-K+-ATPase activity without appreciable vascular effects or effects on barrier permeability, while compound D was found to have a potent effect on the last two parameters without any influence on the first, suggests that products of the cytochrome P450 system are capable of inducing or modulating highly specific functions.
Masferrer
J L
JL
Department of Pharmacology, New York Medical College, Valhalla 10595.
Laniado-Schwartzman
M
M
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000502:physiology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004847:Epithelial Cells; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D001095:Arachidonic Acids; D003577:Cytochrome P-450 Enzyme System; D000254:Sodium-Potassium-Exchanging ATPase