Effect of 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy)chalcone (SU-88) on prostaglandin metabolism in hog gastric mucosa.
SU-88 [2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy)chalcone] inhibited the activity of the prostaglandin (PG)-metabolizing enzyme, 15-hydroxy-PG-dehydrogenase (15-OH-PG-DH), in a cytoplasmic fraction of gastric mucosa. This compound had no effect on the PG synthetase of bovine seminal vesicle microsomes and lactate dehydrogenase in rat liver. The 15-OH-PG-DH activity of gastric mucosa was not influenced by a specific inhibitor of alcohol dehydrogenase, 4-methylpyrazole. Carbenoxolone (CBX) also inhibited 15-OH-PG-DH activity. The IC50 values for SU-88 and CBX were approximately 20 and 40 microM respectively. SU-88 inhibited 15-OH-PG-DH activity uncompetitively or competitively according to whether PGE1 or NAD was used as substrate. CBX inhibited competitively the activity of this enzyme for both substrates. After the addition of SU-88 or CBX to the incubation medium of gastric mucosa, the PGE2 level of the medium was increased significantly while that of the tissue remained unchanged. These results indicate that SU-88 specifically inhibited 15-OH-PG-DH activity and suggest that 15-OH-PG-DH activity regulates the level of PGs in gastric mucosa and may have an anti-ulcer influence.
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002229:Carbenoxolone / Q000494:pharmacology; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology*; D047188:Chalcones; D005753:Gastric Mucosa / Q000378:metabolism*; D006168:Guinea Pigs; D006911:Hydroxyprostaglandin Dehydrogenases / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000201:enzymology; D011427:Propiophenones / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism*; D013552:Swine
D000897:Anti-Ulcer Agents; D047188:Chalcones; D011427:Propiophenones; D011453:Prostaglandins; C035032:sofalcone; D002599:Chalcone; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D002229:Carbenoxolone