Identification of 13,14-dihydro-15-oxo-prostaglandin F2 alpha in the circulation during infusions of bradykinin and prostaglandin E2 in man.
Bradykinin, prostaglandin E2 (PGE2), PGD2 and vehicle (saline) were each administered intravenously on separate occasions to 6 healthy men for a period of 60 min. 13,14-Dihydro-15-oxo-PGF2 alpha was identified in plasma samples obtained during intravenous infusions of bradykinin and PGE2 but not during infusions of PGD2 or saline. The structure of this metabolite was verified by comparison of three different derivatives with authentic standards, using gas chromatography/electron capture mass spectrometry. Bradykinin increased plasma concentrations of 13,14-dihydro-15-oxo-PGF2 alpha from baseline values in the range less than 5-10 pg ml-1 to 28-403 pg ml-1. PGE2 increased plasma concentrations of 13,14-dihydro-15-oxo-PGF2 alpha from baseline values in the range less than 5-17 pg ml-1 to 160-603 pg ml-1. Neither PGD2 nor the vehicle affected 13,14-dihydro-15-oxo-PGF2 alpha concentrations. We conclude that bradykinin-stimulated 13,14-dihydro-15-oxo-PGF2 alpha may be derived from PGE2 or PGF2 alpha. The possibility that these prostaglandins are synthesized by stimulation of microvascular endothelium during bradykinin infusion is discussed.
Barrow
S E
SE
Cockcroft
J
J
Dollery
C T
CT
Hickling
N E
NE
Ritter
J M
JM
D000328:Adult; D001711:Biotransformation; D001920:Bradykinin / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives*; D015232:Dinoprostone; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D011458:Prostaglandins E / Q000378:metabolism*; D011460:Prostaglandins F / Q000097:blood*
D011458:Prostaglandins E; D011460:Prostaglandins F; C008228:15-keto-13,14-dihydroprostaglandin F2alpha; D015237:Dinoprost; D015232:Dinoprostone; D001920:Bradykinin