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

J Lipid Res. 2004 Apr;45(4):757-63. doi: 10.1194/jlr.M300475-JLR200. Epub 2004 Jan 16.

Abstract

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.

MeSH terms

  • Amidohydrolases / deficiency*
  • Amidohydrolases / metabolism
  • Animals
  • Arachidonic Acids / administration & dosage
  • Arachidonic Acids / pharmacokinetics*
  • Biotransformation
  • Chromatography, High Pressure Liquid
  • Cyclooxygenase 2
  • Dinoprostone / analogs & derivatives*
  • Dinoprostone / analysis
  • Dinoprostone / biosynthesis
  • Endocannabinoids
  • Intestine, Small / chemistry
  • Isoenzymes / metabolism
  • Kidney / chemistry
  • Liver / chemistry
  • Lung / chemistry
  • Mass Spectrometry
  • Mice
  • Mice, Knockout
  • Polyunsaturated Alkamides
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Prostaglandins / analysis
  • Prostaglandins / biosynthesis*
  • Tissue Distribution

Substances

  • Arachidonic Acids
  • Endocannabinoids
  • Isoenzymes
  • Polyunsaturated Alkamides
  • Prostaglandins
  • prostaglandin D2 ethanolamide
  • prostaglandin E2 ethanolamide
  • prostaglandin F2alpha ethanolamide
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Amidohydrolases
  • fatty-acid amide hydrolase
  • Dinoprostone
  • anandamide