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Papers In Press, published online ahead of print January 16, 2004
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Pharmacokinetics and Drug Metabolism, Allergan, Irvine, CA 92612-1599
Corresponding Author: weber_allan{at}allergan.com
The in vitro formation of PGE2 1-ethanolamide by cyclooxygenase-2 (COX-2) has been reported. We investigated the formation of prostamides F2a, E2, and D2 (PGF2a 1-ethanolamide, PGE2 1-ethanolamide and PGD2 1-ethanolamide respectively) in liver, lung, kidney and small intestine after a single intravenous bolus administration of 50 mg/kg of anandamide to normal and fatty acid amide hydrolase (FAAH) knockout male (FAAH -/-) mice. Three FAAH -/- mice and six normal mice were used in the study. One group of 3 normal mice was not dosed (naïve) while the other group of 3 normal mice received a bolus intravenous injection of 50 mg/kg of anandamide (treated controls). The FAAH -/- mice also received an intravenous injection of 50 mg/kg of anandamide (treated FAAH -/-). After 30 minutes, the lung, liver, kidney and small intestine were harvested and processed by liquid-liquid extraction. The concentrations of prostamide F2a, prostamide E2, prostamide D2 and anandamide were determined by high performance liquid chromatography-tandem mass spectrometry using multiple reaction monitoring mode . The results indicated that prostamide F2a could be detected in tissues in FAAH -/- mice after administration of anandamide. Concentrations of anandamide, prostamide E2 and prostamide D2 in liver, kidney, lung and small intestine were much higher in the anandamide treated FAAH -/- mice than those of the anandamide treated control mice. This is the first report demonstrating that prostamides including prostamide F2a were formed in vivo from anandamide potentially by the COX-2 pathway when the competing FAAH pathway is lacking.
Revised on January 16, 2004
Accepted on January 13, 2004
Formation of prostamides from anandamide in FAAH knockout mice analyzed by HPLC with tandem mass spectrometry
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