Hepatic metabolism of prostacyclin (PGI2) in the rabbit: formation of a potent novel inhibitor of platelet aggregation.
Hepatic metabolism of prostacyclin (PGI2) in the rabbit: formation of a potent novel inhibitor of platelet aggregation.
复制标题
兔中前列环素 (PGI2) 的肝代谢：形成一种有效的新型血小板聚集抑制剂。
DOI：
10.1016/0006-291x(80)91103-1
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发表时间：
1980
影响因子：
3.1
通讯作者：
Frank F. Sun
中科院分区：
文献类型：
--
作者：
Patrick Y.;Kafait U. Malik;Dominic M. Desiderio;J. Mcgiff;Frank F. Sun
Metabolism of [9-3H]-PGI2was studied in the isolated Tyrode's perfused rabbit liver. Five products, four radioactive and one non-radioactive, were identified in the perfusate: 19-hydroxy-6-keto-PGF1α, 6-keto-PGF1α, dinor-6-keto-PGF1α, pentanor PGF1αand a 6-keto-PGE1-like substance. The first two, 19-hydroxy-6-keto-PGF1αand 6-keto-PGF1α, represented 5% and 45% respectively, of the total radioactivity; the last two accounted for 39%. The presence of dinor and pentanor derivatives of 6-keto-PGF1αindicated that β -oxidation and oxidative-decarboxylation occurs in the liver as the major metabolic pathway of PGI2. One non-radioactive metabolite which co-migrated with authentic 6-keto-PGE1was found to inhibit platelet aggregation, having a potency similar to authentic 6-keto-PGE1, and its effect can be eliminated by boiling and by alkali treatment. This metabolite, having similar Rf value on TLC and biological behavior as 6-keto-PGE1, may arise from oxidation of 6-keto-PGF1αvia the 9-hydroxyprostaglandin dehydrogenase pathway, as suggested by recovery of tritiated water in the aqueous phase of the perfusate. This material, a potent inhibitor of platelet aggregation, may arise from PGI2or its hydrolysis product, 6-keto-PGF1α.
