Cited by 2,913Cannabis and Cannabinoid ResearchFatty Acid Research and HealthEicosanoids and Hypertension Pharmacology

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

Mechoulam, Raphael, Ben-Shabat, Shimon, Hanus, Lumir, Ligumsky, Moshe, Kaminski, Norbert E., Schatz, Anthony R., Gopher, Asher, Almog, Shlomo +7 more·1995·Biochemical Pharmacology

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.

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Crossref · 10.1016/0006-2952(95)00109-d

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42 of 42 references verified0 citation errors · 0 not checkable

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  • The most studied endogenous ligands that bind cannabinoid receptors are AEA and 2-AG.

    “The most studied endogenous ligands that bind cannabinoid receptors are AEA (Devane et al, 1992) and 2arachidonoylglycerol (2-AG) (Mechoulam et al, 1995;Sugiura et al, 1995).”
  • AEA actions are not restricted to CB1R; ECBs also act at CB2R, GPR55, TRPV1, and other G protein subtypes such as Gs and/or Gq11.

    “Enriching the picture further, the actions of AEA are not restricted to CB1R, given that ECBs also act, sometimes in a non-retrograde manner, at CB2R [30], GPR55 [31], and TRPV1 (transient receptor potential vanilloid type 1) channels [32–34], as well as other G protein subtypes such as Gs and/or Gq11 [35,36].”

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Authors
Mechoulam, R., Ben-Shabat, S., Hanus, L., Ligumsky, M., Kaminski, N. E., Schatz, A. R., Gopher, A., Almog, S., Martin, B. R., Compton, D. R., Pertwee, R. G., Griffin, G., Bayewitch, M., Barg, J., & Vogel, Z.
Affiliations
  • Hebrew University of Jerusalem (IL)
  • Michigan State University (US)
  • Virginia Commonwealth University (US)
  • Sheba Medical Center (IL)
  • University of Aberdeen (GB)
  • Weizmann Institute of Science (IL)
Corresponding author
Mechoulam, Raphael
Venue
Biochemical Pharmacology
Publisher
Elsevier BV
Published
1995-06
Volume
50
Issue
1
Pages
83-90
ISSN
0006-2952 (ISSN-L)
OpenAlex
W2024653583
Cited by
2,913
References
42
Citations by year
2026: 27 · 2025: 69 · 2024: 89 · 2023: 84 · 2022: 103 · 2021: 125 · 2020: 118 · 2019: 110 · 2018: 89 · 2017: 105 · 2016: 112 · 2015: 109 · 2014: 98 · 2013: 104 · 2012: 137
FWCI
22.43
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Wellcome Trust
  • National Institutes of Health (5r01da008169-02)
  • U.S. Public Health Service
  • National Institute on Drug Abuse (DA 8169, DA-3672)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords
2-arachidonoylglycerol, endocannabinoids, cannabinoid receptors, CB1 receptor, CB2 receptor, canine intestine, adenylate cyclase inhibition, forskolin, delta-9-tetrahydrocannabinol, antinociception, immobility, hypothermia, vas deferens contraction, structure elucidation
MeSH terms
Animals, Arachidonic Acids, Cannabinoids, Cell Line, Dogs, Glycerides, Intestines, Male, Gas Chromatography-Mass Spectrometry, Mice, Inbred ICR, Receptors, Drug, Molecular Structure, Receptors, Cannabinoid, Mice, Endocannabinoids

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