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

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

Journal of Lipid Research (Apr 2004)

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

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

Affiliations

Allan Weber: 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
Jinsong Ni: 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
Kah-Hiing John Ling: 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
Andrew Acheampong: 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
Diane D-S. Tang-Liu: 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
Robert Burk: 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
Benjamin F. Cravatt: 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
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

Journal volume & issue: Vol. 45, no. 4
pp. 757 – 763

Abstract

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We investigated the formation of PGF2α 1-ethanolamide, PGE2 1-ethanolamide, and PGD2 1-ethanolamide (prostamides F2α, 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 F2α, prostamide E2, prostamide D2, and anandamide were determined by HPLC-tandem mass spectrometry. Prostamide F2α 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 F2α, were formed in vivo from anandamide, potentially by the cyclooxygenase-2 pathway when the competing FAAH pathway is lacking.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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