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

Cite this

MECHOULAM, R., BENSHABAT, S., HANUS, L., LIGUMSKY, M., KAMINSKI, N. E., SCHATZ, A. R., GOPHER, A., ALMOG, S., COMPTON, D. R., Pertwee, R. G., GRIFFIN, G., BAYEWITCH, M., BARG, J., VOGEL, Z., & Martin, B. R. (1995). IDENTIFICATION OF AN ENDOGENOUS 2-MONOGLYCERIDE, PRESENT IN CANINE GUT, THAT BINDS TO CANNABINOID RECEPTORS. Biochemical Pharmacology, 50(1), 83-90. https://doi.org/10.1016/0006-2952(95)00109-D