Inhibition of the human placental NAD- and NADP-linked 15-hydroxyprostaglandin dehydrogenases by nonsteroidal anti-inflammatory drugs.
A number of nonsteroidal anti-inflammatory drugs are non-competitive or mixed inhibitors of human placental NAD- and NADP-linked 15-hydroxyprostaglandin dehydrogenases. Cis- and trans-sulindac sulfide and cis- and trans-sulindac inhibit the NAD-linked enzyme as well or better than they inhibit various cyclooxygenases in vitro. The remainder of the compounds tested are at least one order of magnitude less effective as inhibitors of the 15-hydroxyprostaglandin dehydrogenases than they are as inhibitors of cyclooxygenases. Cis- and trans-sulindac sulfide are sufficiently strong inhibitors of the NAD-linked enzyme (Kis of 7.8 microM and 6.8 microM respectively) to raise the possibility that they might also inhibit this enzyme in vivo.
Jarabak
J
J
Department of Medicine, University of Chicago School of Medicine, Illinois 60637.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors*; D007213:Indomethacin / Q000494:pharmacology; D009243:NAD / Q000494:pharmacology*; D009249:NADP / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology*; D011225:Pre-Eclampsia / Q000201:enzymology; D011247:Pregnancy; D013237:Stereoisomerism; D013467:Sulindac / Q000031:analogs & derivatives / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009243:NAD; D013467:Sulindac; D009249:NADP; C025462:sulindac sulfide; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D007213:Indomethacin