Enzymes of porcine brain hydrolyzing 2-arachidonoylglycerol, an endogenous ligand of cannabinoid receptors

Biochem Pharmacol. 1999 Feb 15;57(4):417-23. doi: 10.1016/s0006-2952(98)00314-1.

Abstract

Anandamide and 2-arachidonoylglycerol (2-AG) are two endogenous ligands for the cannabinoid receptors, and their cannabimimetic activities are lost when they are hydrolyzed enzymatically. Cytosol and particulate fractions of porcine brain exhibited a high 2-AG hydrolyzing activity of 100 nmol/min/mg protein. Most of the activity could be attributed to a monoacylglycerol lipase-like enzyme that did not hydrolyze anandamide. It was separated by hydroxyapatite chromatography from anandamide amidohydrolase, which is also capable of hydrolyzing 2-AG as well as anandamide. Thus, porcine brain has at least two enzymes capable of hydrolyzing 2-AG. The 2-AG hydrolase activities of both the cytosolic and particulate enzymes were irreversibly and time-dependently inhibited by methyl arachidonyl fluorophosphonate with IC50 values as low as 2-3 nM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / metabolism
  • Animals
  • Arachidonic Acids / metabolism
  • Arachidonic Acids / pharmacology
  • Brain / enzymology*
  • Cytosol / enzymology
  • Endocannabinoids
  • Enzyme Inhibitors / pharmacology
  • Glycerides / metabolism*
  • Hydrogen-Ion Concentration
  • Ligands
  • Monoacylglycerol Lipases / antagonists & inhibitors
  • Monoacylglycerol Lipases / isolation & purification
  • Monoacylglycerol Lipases / metabolism*
  • Organophosphonates / pharmacology
  • Polyunsaturated Alkamides
  • Receptors, Cannabinoid
  • Receptors, Drug / metabolism*
  • Substrate Specificity
  • Swine

Substances

  • Arachidonic Acids
  • Endocannabinoids
  • Enzyme Inhibitors
  • Glycerides
  • Ligands
  • Organophosphonates
  • Polyunsaturated Alkamides
  • Receptors, Cannabinoid
  • Receptors, Drug
  • methyl arachidonylfluorophosphonate
  • glyceryl 2-arachidonate
  • Monoacylglycerol Lipases
  • Amidohydrolases
  • fatty-acid amide hydrolase
  • anandamide