Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors
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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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).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Mechoulam 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].”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [30]
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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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