Communication
NADP-linked 15-hydroxyprostaglandin dehydrogenase for prostaglandin D2 in human blood platelets

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Abstract

Two forms of NADP-linked 15-hydroxyprostaglandin dehydrogenase for prostaglandin D2 were found in the cytosol fraction of human blood platelets. These enzymes were purified by ammonium sulfate fractionation, Blue Sepharose, and Sephadex G-100 column chromatography. The two enzymes differed in molecular weights (65,000 for peak I enzyme and 31,000 for peak II as estimated by gel filtration) and their substrate specificities. The relative rates for reaction with peak I enzyme were: prostaglandin D2, 100(%); E2, 14; F, 2; I2, 29; and B2, 0; whereas for peak II enzyme, D2, 100; E2, 23; F, 61; I2, 29; and B2, 131. Prostaglandin D2 was converted to 15-ketoprostaglandin D2 and then 13,14-dihydro-15-ketoprostaglandin D2, which were identified by spectrophotometry and gas chromatography/mass spectrometry, respectively. These metabolites were three orders of magnitude less potent in inhibiting human platelet aggregation than prostaglandin D2. The results indicated that NADP-linked dehydrogenases participated in the metabolic inactivation of prostaglandin D2 in the platelets. Furthermore, the dehydrogenase activity for prostaglandin D2 was high in monkey (0.128 nmol/min · mg at 24 °C) and human platelets (0.066), but was not detectable (less than 0.007) in the rabbit, rat, and chicken. Because prostaglandin D2, which was demonstrated by several authors to be synthesized in platelet-rich plasma during platelet aggregation, exhibited significant antiaggregatory activity only in human and monkey platelets, these prostaglandin dehydrogenases appear to play a physiological role in the circulatory system.

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    This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, and by grants from the Japanese Foundation on Metabolism and Diseases, Research Foundation for Cancer and Cardiovascular Diseases, Fujiwara Memorial Foundation, Wellcome Foundation, and Mitsui Life Social Welfare Foundation.

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