Hepatic metabolism of prostacyclin (PGI2) in the rabbit

Formation of a potent novel inhibitor of platelet aggregation

Patrick Y.K. Wong, Kafait Malik, Dominic M. Desiderio, John C. McGiff, Frank F. Sun

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Metabolism of [9-3H]-PGI2 was 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-PGF, 6-keto-PGF, dinor-6-keto-PGF, pentanor PGF and a 6-keto-PGE1-like substance. The first two, 19-hydroxy-6-keto-PGF and 6-keto-PGF, 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-PGF indicated 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-PGE1 was 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-PGF via 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 PGI2 or its hydrolysis product, 6-keto-PGF.

Original languageEnglish (US)
Pages (from-to)486-494
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume93
Issue number2
DOIs
StatePublished - Mar 28 1980

Fingerprint

Platelet Aggregation Inhibitors
Epoprostenol
Metabolism
Rabbits
Liver
prostaglandin-E2 9-reductase
Metabolites
prostaglandin F1
Oxidation
Decarboxylation
Radioactivity
Alkalies
Platelets
Metabolic Networks and Pathways
Platelet Aggregation
Boiling liquids
Hydrolysis
Agglomeration
Derivatives
Recovery

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Hepatic metabolism of prostacyclin (PGI2) in the rabbit : Formation of a potent novel inhibitor of platelet aggregation. / Wong, Patrick Y.K.; Malik, Kafait; Desiderio, Dominic M.; McGiff, John C.; Sun, Frank F.

In: Biochemical and Biophysical Research Communications, Vol. 93, No. 2, 28.03.1980, p. 486-494.

Research output: Contribution to journalArticle

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