IDENTIFICATION OF AN ENDOGENOUS 2-MONOGLYCERIDE, PRESENT IN CANINE GUT, THAT BINDS TO CANNABINOID RECEPTORS

R MECHOULAM, S BENSHABAT, L HANUS, M LIGUMSKY, N E KAMINSKI, A R SCHATZ, A GOPHER, S ALMOG, D R COMPTON, Roger Guy Pertwee, G GRIFFIN, M BAYEWITCH, J BARG, Z VOGEL, Billy R. Martin

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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 K-i 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.

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

Keywords

  • 2-ARACHIDONYL GLYCEROL
  • ANAND AMIDE
  • TETRAHYDROCANNABINOL
  • ARACHIDONYLETHANOLAMIDE
  • IMMUNE SYSTEM
  • TRANSFECTION
  • MOUSE BEHAVIOR
  • ADENYLATE CYCLASE INHIBITION
  • MOUSE SPLEEN-CELLS
  • CANNABIMIMETIC AGENTS
  • BRAIN CONSTITUENT
  • ADENYLATE-CYCLASE
  • ANANDAMIDE
  • DELTA-9-TETRAHYDROCANNABINOL
  • EXPRESSION
  • INHIBITION
  • AGONIST
  • 2-arachidonyl glycerol
  • tetrahydrocannabinol
  • anandamide
  • arachidonylethanolamide
  • immune system
  • transfection
  • mouse behavior
  • adenylate cyclase inhibition

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