Expression of gastric antisecretory and prostaglandin E receptor binding activity of misoprostol by misoprostol free acid.
In enriched canine parietal cell preparations, misoprostol, an analog of prostaglandin E1 methyl ester, was rapidly deesterified to misoprostol free acid. Under this circumstance, misoprostol and misoprostol free acid exhibited equal antisecretory potency against histamine-stimulated acid secretion and bound equally well to prostaglandin E receptors. When the deesterification of misoprostol was inhibited by paraoxon, an esterase inhibitor, the antisecretory and receptor binding activity of misoprostol was markedly reduced, with potency much less than misoprostol free acid. These results indicate that misoprostol free acid is the active biological form of misoprostol that binds to prostaglandin E receptors and mediates the antisecretory action of misoprostol.
Tsai
B S
BS
Gastrointestinal Diseases Research, Searle Research and Development, Skokie, Illinois 60077.
Kessler
L K
LK
Stolzenbach
J
J
Schoenhard
G
G
Bauer
R F
RF
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004951:Esterification / Q000187:drug effects; D066298:In Vitro Techniques; D016595:Misoprostol; D010261:Paraoxon / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000187:drug effects*; D011458:Prostaglandins E / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D018078:Receptors, Prostaglandin E
D000897:Anti-Ulcer Agents; D011458:Prostaglandins E; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D016595:Misoprostol; D000527:Alprostadil; D010261:Paraoxon