Molecular characterization of a peripheral receptor for cannabinoids
Abstract
The major active ingredient of marijuana, delta 9-tetrahydrocannabinol (delta 9-THC), has been used as a psychoactive agent for thousands of years. Marijuana, and delta 9-THC, also exert a wide range of other effects including analgesia, anti-inflammation, immunosuppression, anticonvulsion, alleviation of intraocular pressure in glaucoma, and attenuation of vomiting. The clinical application of cannabinoids has, however, been limited by their psychoactive effects, and this has led to interest in the biochemical bases of their action. Progress stemmed initially from the synthesis of potent derivatives of delta 9-THC, and more recently from the cloning of a gene encoding a G-protein-coupled receptor for cannabinoids. This receptor is expressed in the brain but not in the periphery, except for a low level in testes. It has been proposed that the nonpsychoactive effects of cannabinoids are either mediated centrally or through direct interaction with other, non-receptor proteins. Here we report the cloning of a receptor for cannabinoids that is not expressed in the brain but rather in macrophages in the marginal zone of spleen.
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THC and certain other plant-derived or synthetic psychoactive cannabinoids bind CB1 and CB2 receptors.
“The primary psychoactive constituent of cannabis, THC (Mechoulam and Gaoni, 1965), and certain other plant-derived or synthetic psychoactive cannabinoids bind cannabinoid (CB 1 and CB 2 ) receptors (Devane et al, 1988;Matsuda et al, 1990;Munro et al, 1993).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Munro et al, 1993
CB1 and CB2 receptors exhibit disparate anatomical distributions.
“CB1 and CB2 receptors exhibit disparate anatomical distributions.3”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [3]
Both CB1 and CB2 receptors are G-protein-coupled receptors that are negatively coupled to adenylate cyclase.
“Both CB12 and CB23 receptors are G-coupled protein receptors that are negatively coupled to adenylate cyclase.”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [3]
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- Authors
- Munro, S., Thomas, K. L., & Abu-Shaar, M.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Venue
- Nature
- Published
- 1993-09
- Volume
- 365
- Issue
- 6441
- Pages
- 61-65
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2056188558
- Cited by
- 5,092
- References
- 30
- Citations by year
- 2026: 76 · 2025: 119 · 2024: 165 · 2023: 172 · 2022: 198 · 2021: 244 · 2020: 212 · 2019: 184 · 2018: 169 · 2017: 188 · 2016: 182 · 2015: 175 · 2014: 188 · 2013: 201 · 2012: 202
- FWCI
- 39.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- cannabinoid receptors, delta-9-tetrahydrocannabinol, peripheral cannabinoid receptors, macrophages, receptor cloning, G protein-coupled receptors, immunosuppression, anti-inflammatory activity
- MeSH terms
- Amides, Amino Acid Sequence, Animals, Arachidonic Acids, Base Sequence, Brain, Cannabinoids, Cloning, Molecular, DNA, Fatty Acids, Unsaturated, Humans, Macrophages, Molecular Sequence Data, Morpholines, Naphthalenes, Receptors, Drug, RNA, Spleen, Tumor Cells, Cultured, Receptors, Cannabinoid, Benzoxazines, Rats, Polyunsaturated Alkamides, Endocannabinoids
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