RT Journal Article SR Electronic T1 Inhibition of 15-Hydroxyprostaglandin Dehydrogenase by 9,11-Deoxyprostaglandins in Vitro and in Vivo JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 456 OP 462 VO 19 IS 3 A1 MITSUO YAMAZAKI A1 KAZUO OHUCHI A1 MASAAKI SASAKI A1 KIYOSHI SAKAI YR 1981 UL http://molpharm.aspetjournals.org/content/19/3/456.abstract AB Fourty-six prostaglandin analogues were studied to determine their ability to inhibit 15-hydroxyprostaglandin dehydrogenase partially purified from swine lung. The inhibition was high in prostaglandin analogues having the following structure: (a) cyclopentane ring with no substituent; (b) hydroxy or keto group at carbon atom 15: (c) lengths of side chains similar to those of prostaglandin: and (d) methylene group between carbon atoms 13 and 14. The most potent inhibitor was rac-13β,14β-methylene-15-ketoprostanoate, the Ki being 0.14 µM, and its inhibition was noncompetitive with regard to prostaglandin (PG) E2, the substrate. This compound inhibited [3H]PGE1 degradation in the soluble fraction of guinea pig lung homogenates. One potent inhibitor, 15α-hydroxyprost-13-enoate (9,11-deoxy-PGE1), was tested for its in vivo effect in anesthetized rats. When PGE1 was intravenously infused together with 9,11-deoxy-PGE1, its antilipolytic activity was significantly enhanced. Namely, the blood free fatty acid levels, which had been elevated by norepinephrine injection, were markedly decreased by the infusions of PGE1 with the inhibitor.