Inhibition of prostaglandin biosynthesis by a new anti-inflammatory drug, TA-60.
Effect of a new anti-inflammatory drug which has a little ulcer inducing property on gastrointestinal tract, TA-60 (2-[4-(3-methyl-2-butenyl) phenyl] propionic acid), on the prostaglandin (PG) metabolism was investigated. TA-60 inhibited the PGE2 biosynthesis of the bovine seminal vesicle microsome dose-dependently. The inhibition constant (Ki) of TA-60 was approximately 8 microM. The potency of TA-60 was approximately the same and two times that of ibuprofen (IP) and phenylbutazone (PBZ), respectively. TA-60 did not show the time dependent inhibition of the PGE2 biosynthesis unlikely to indomethacin (IM). The decrease in the PGE2 contents in the stomach of the rats by TA-60 reached a plateau and the content was not decreased to less than a certain level. The PGE2 content of the intestine was not changed by TA-60. TA-60 did not inhibit the activity of the PG degradating enzyme, 15-hydroxy PG dehydrogenase (15-OH-PG-DH) of the gastric mucosa like the other non-steroidal anti-inflammatory drugs (NSAIDs): IP, PBZ and IM. These results suggest that the slight ulcerating effect of TA-60 on the gastrointestinal tract might be resulted from the small decreasing effect of TA-60 on the gastrointestinal level of PGE2.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001665:Binding Sites; D002417:Cattle; D016861:Cyclooxygenase Inhibitors; D003864:Depression, Chemical; D004064:Digestive System / Q000032:analysis / Q000187:drug effects; D015232:Dinoprostone; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors; D008297:Male; D010666:Phenylpropionates / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D013237:Stereoisomerism
D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D010666:Phenylpropionates; D011453:Prostaglandins; D011458:Prostaglandins E; C045803:2-(4-(3-methyl-2-butenyl)phenyl)propionic acid; D006911:Hydroxyprostaglandin Dehydrogenases; D015232:Dinoprostone