Oxidative metabolism of dihomogammalinolenic acid by guinea pig epidermis: evidence of generation of anti-inflammatory products.
Reports that vegetable oils which contain gamma-linolenic acid (18:3n-6) may exert beneficial effects on cutaneous disorders prompted us to investigate whether epidermis possesses the ability to transform dihomogammalinolenic acid (20:3n-6), the epidermal elongase product of 18:3n-6, into oxidative metabolites with anti-inflammatory potential. Incubations of [1-14C]20:3n-6 with the 105,000 g particulate (microsomal) fraction from guinea pig epidermal homogenate resulted in the formation of the 1-series prostaglandin PGE1. The identity of this product was confirmed by argentation thin-layer chromatography (TLC), reverse phase-HPLC, and conversion with alkali treatment to PGB1. Incubations of [1-14C]20:3n-6 with the 105,000 g supernatant (cytosolic) fraction from guinea pig epidermal homogenate resulted in the formation of the 15-lipoxygenase product 15-hydroxy-8, 11, 13-eicosatrienoic acid (15-OH-20:3n6). The identity of this product was confirmed by normal phase-HPLC and gas chromatography/mass spectrometry (GC/MS). Thus, data from these studies indicate the capacity of enzymes in the microsomal and cytosolic fractions of guinea pig epidermal homogenates to transform 20:3n-6 to the eicosanoids PGE1 and 15-OH 20:3n-6, products which reportedly have anti-inflammatory properties. The in vivo significance of these findings remains to be explored.
D015126:8,11,14-Eicosatrienoic Acid / Q000378:metabolism*; D000527:Alprostadil / Q000378:metabolism; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000097:blood; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001792:Blood Platelets / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D004817:Epidermis / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006168:Guinea Pigs; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011456:Prostaglandins B / Q000378:metabolism; D051381:Rats
D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D011456:Prostaglandins B; C034467:prostaglandin B1; D001092:Arachidonate 12-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D000527:Alprostadil; D015126:8,11,14-Eicosatrienoic Acid