Formation of prostamides from anandamide in FAAH knockout mice analyzed by HPLC with tandem mass spectrometry.
We investigated the formation of PGF(2alpha) 1-ethanolamide, PGE(2) 1-ethanolamide, and PGD(2) 1-ethanolamide (prostamides F(2alpha), E(2), and D(2), 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 F(2alpha), prostamide E(2), prostamide D(2), and anandamide were determined by HPLC-tandem mass spectrometry. Prostamide F(2alpha) was detected in tissues in FAAH -/- mice after administration of anandamide. Concentrations of anandamide, prostamide E(2), and prostamide D(2) 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 F(2alpha), were formed in vivo from anandamide, potentially by the cyclooxygenase-2 pathway when the competing FAAH pathway is lacking.
Weber
Allan
A
Department of Pharmacokinetics and Drug Metabolism, Allergan, Inc., 2525 Dupont Drive, P.O. Box 19534, Irvine, CA 92623, USA. weber_allan@allergan.com
Ni
Jinsong
J
Ling
Kah-Hiing John
KH
Acheampong
Andrew
A
Tang-Liu
Diane D-S
DD
Burk
Robert
R
Cravatt
Benjamin F
BF
Woodward
David
D
D000581:Amidohydrolases / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis; D063388:Endocannabinoids; D007421:Intestine, Small / Q000737:chemistry; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D053284:Polyunsaturated Alkamides; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000032:analysis / Q000096:biosynthesis*; D014018:Tissue Distribution; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D063388:Endocannabinoids; D007527:Isoenzymes; D053284:Polyunsaturated Alkamides; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins; D000099252:Fatty Acid Amide Hydrolases; C493493:prostaglandin D2 ethanolamide; C107684:prostaglandin E2 ethanolamide; C493494:prostaglandin F2alpha ethanolamide; C078814:anandamide