Endogenous inhibitor of 15-hydroxyprostaglandin dehydrogenase in human placenta.
An endogenous inhibitor of NAD-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) in human placenta has been anticipated, but not yet isolated. In this study, we used acetone to extract an inhibitor of PGDH from a 10,000/g supernatant fraction of human placenta and partially purified it by precipitation at pH 5.2. The inhibitor was heat stable and resistant to trypsin, but easily inactivated by lipase treatment. It appears to be a kind of lipid with a low molecular mass of less than 1000 daltons. Inhibitory activity showed pH dependency with an inhibitory peak at pH 11 and a plateau from pH 8.0 to 9.0. The pattern of inhibition was competitive with regard to PGE2 and uncompetitive with regard to NAD at pH 8.0. The Ki value for PGE2 was calculated to be 18.9 microM. This endogenous inhibitor may have an important role in prostaglandin catabolism in human placenta.
Nagai
K
K
Department of Obstetrics & Gynecology, Miyazaki Medical College, Japan.
Mibe
M
M
Mori
N
N
D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D066298:In Vitro Techniques; D007700:Kinetics; D010920:Placenta / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy
D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D015232:Dinoprostone