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.