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Journal of Lipid Research, Vol. 45, 757-763, April 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Formation of prostamides from anandamide in FAAH knockout mice analyzed by HPLC with tandem mass spectrometry

Allan Weber^1,*, Jinsong Ni^*, Kah-Hiing John Ling^*, Andrew Acheampong^*, Diane D-S. Tang-Liu^*, Robert Burk, Benjamin F. Cravatt and David Woodward^**

^* Department of Pharmacokinetics and Drug Metabolism, Allergan, Inc., 2525 Dupont Drive, P.O. Box 19534, Irvine, CA 92623
^** Department of Biological Sciences, Allergan, Inc., 2525 Dupont Drive, P.O. Box 19534, Irvine, CA 92623
Department of Medicinal Chemistry, Allergan, Inc., 2525 Dupont Drive, P.O. Box 19534, Irvine, CA 92623
The Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037

¹ To whom correspondence should be addressed. e-mail: weber_allan{at}allergan.com

We investigated the formation of PGF₂ 1-ethanolamide, PGE₂ 1-ethanolamide, and PGD₂ 1-ethanolamide (prostamides F₂, E₂, and D₂, 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 knockout (FAAH -/-) male mice. One group of three normal mice was not dosed (naïve) while another group of three normal mice received a bolus intravenous injection of 50 mg/kg of anandamide. Three FAAH -/- mice also received an intravenous injection of 50 mg/kg of anandamide. After 30 min, the lung, liver, kidney, and small intestine were harvested and processed by liquid-liquid extraction. The concentrations of prostamide F₂, prostamide E₂, prostamide D₂, and anandamide were determined by HPLC-tandem mass spectrometry. Prostamide F₂ was 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 report demonstrates that prostamides, including prostamide F₂, were formed in vivo from anandamide, potentially by the cyclooxygenase-2 pathway when the competing FAAH pathway is lacking.

Abbreviations: COX-2, cyclooxygenase-2; FAAH, fatty acid amide hydrolase; FAAH -/-, FAAH knockout; HPLC-MS/MS, HPLC tandem mass spectrometry; LC-MS/MS, liquid chromatography-MS/MS; MRM, multiple-reaction monitoring; prostamide D₂, PGD₂ 1-ethanolamide; prostamide E₂, PGE₂ 1-ethanolamide; prostamide F₂, PGF₂ 1-ethanolamide

Supplementary key words anandamide • cyclooxygenase-2 • fatty acid amide hydrolase • high-performance liquid chromatography • PGD₂ 1-ethanolamide • PGE₂ 1-ethanolamide • PGF₂ 1-ethanolamide • prostamide D₂ • prostamide E₂ • prostamide F₂

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