In vivo assessment of precursor induced prostaglandin release within the rat gastric lumen.
Gastroprotection associated with the intragastric administration of prostaglandin (PG) precursor fatty acids such as linoleic (LA), gamma-linolenic (GLA), and arachidonic acid (AA) has been reported to be mediated via their conversion to PGs. This report examines the relationship between gastroprotection and the extent/rate of PG-release in rats intragastrically administered PG biosynthetic precursors: LA, AA, dihomo-gamma-linolenic acid (DHGL) or oleic acid (OA, a nonprecursor fatty acid). At various times following intragastric administration of a fatty acid, gastric fluid was collected, extracted, chromatographed, and assayed for PGE1 or PGE2 by specific radioimmunoassay. AA and DHGL dose dependently elevated gastric PGE2 and PGE1 levels, respectively. Maximal PGE elevation, 200-400 ng/stomach, was over 400-fold above basal values, and observed within 5-10 minutes of administration. Conversely, OA and LA elicited only a minor (2-10 fold) stimulation of PGE release. In contrast to effects on PG release, all four fatty acids protected the gastric mucosa against macroscopic damage induced by ethanol. The apparent rank order of potency was AA greater than DHGL = LA greater than OA (the difference in potency between DHGL or LA and OA was not significant). Since LA and OA (a nonprecursor) only marginally elevated lumenal PGs relative to DHGL or AA, yet were equally efficacious in the gastroprotection assay, it is likely that other fatty acid-related mechanisms play an important role in protecting the stomach against ethanol-induced injury.
Doyle
M J
MJ
Procter and Gamble Company, Miami Valley Laboratories, Cincinnati, Ohio 45239-8707.
Nemeth
P R
PR
Skoglund
M L
ML
Mandel
K G
KG
D000818:Animals; D000897:Anti-Ulcer Agents; D001095:Arachidonic Acids / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005227:Fatty Acids / Q000302:isolation & purification / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D007441:Intubation, Gastrointestinal; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced / Q000503:physiopathology
D000897:Anti-Ulcer Agents; D001095:Arachidonic Acids; D005227:Fatty Acids; D011453:Prostaglandins; D015232:Dinoprostone