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

Raphael Mechoulam, Shimon Ben-Shabat, Lumir Hanus, Moshe Ligumsky, Norbert E. Kaminski, Anthony R. Schatz, Asher Gopher, Shlomo Almog, Billy R. Martin, David R. Compton, Roger G. Pertwee, Graeme Griffin, Michael Bayewitch, Jacob Barg, Zvi Vogel

Research output: Contribution to journalArticlepeer-review

2450 Scopus citations

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 Δ9-tetrahydrocannabinol (Δ9-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 Δ9-THC to inhibit electrically evoked contractions of mouse isolated vasa deferentia; however, it was less potent than Δ9-THC.

Original languageEnglish
Pages (from-to)83-90
Number of pages8
JournalBiochemical Pharmacology
Volume50
Issue number1
DOIs
StatePublished - 29 Jun 1995
Externally publishedYes

Keywords

  • 2-arachidonyl glycerol
  • adenylate cyclase inhibition
  • anandamide
  • arachidonylethanolamide
  • immune system
  • mouse behavior
  • tetrahydrocannabinol
  • transfection

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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