Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors

Biochem Pharmacol. 1995 Jun 29;50(1):83-90. doi: 10.1016/0006-2952(95)00109-d.

Abstract

In this study, we report the isolation from canine intestines of 2-arachidonyl glycerol (2-Ara-Gl). Its structure was determined by mass spectrometry and by direct comparison with a synthetic sample. 2-Ara-Gl bound to membranes from cells transiently transfected with expression plasmids carrying DNA of either CB1 or CB2--the two cannabinoid receptors identified thus far--with Ki values of 472 +/- 55 and 1400 +/- 172 nM, respectively. In the presence of forskolin, 2-Ara-Gl inhibited adenylate cyclase in isolated mouse spleen cells, at the potency level of delta 9-tetrahydrocannabinol (delta 9-THC). Upon intravenous administration to mice, 2-Ara-Gl caused the typical tetrad of effects produced by THC: antinociception, immobility, reduction of spontaneous activity, and lowering of the rectal temperature. 2-Ara-Gl also shares the ability of delta 9-THC to inhibit electrically evoked contractions of mouse isolated vasa deferentia; however, it was less potent than delta 9-THC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arachidonic Acids*
  • Cannabinoids / agonists
  • Cell Line
  • Dogs
  • Endocannabinoids
  • Gas Chromatography-Mass Spectrometry
  • Glycerides / chemistry
  • Glycerides / metabolism*
  • Glycerides / pharmacology
  • Intestines / chemistry*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Molecular Structure
  • Receptors, Cannabinoid
  • Receptors, Drug / metabolism*

Substances

  • Arachidonic Acids
  • Cannabinoids
  • Endocannabinoids
  • Glycerides
  • Receptors, Cannabinoid
  • Receptors, Drug
  • glyceryl 2-arachidonate