The orphan receptor GPR55 is a novel cannabinoid receptor
Open accessAbstract
BACKGROUND: The endocannabinoid system functions through two well characterized receptor systems, the CB1 and CB2 receptors. Work by a number of groups in recent years has provided evidence that the system is more complicated and additional receptor types should exist to explain ligand activity in a number of physiological processes. EXPERIMENTAL APPROACH: Cells transfected with the human cDNA for GPR55 were tested for their ability to bind and to mediate GTPgammaS binding by cannabinoid ligands. Using an antibody and peptide blocking approach, the nature of the G-protein coupling was determined and further demonstrated by measuring activity of downstream signalling pathways. KEY RESULTS: We demonstrate that GPR55 binds to and is activated by the cannabinoid ligand CP55940. In addition endocannabinoids including anandamide and virodhamine activate GTPgammaS binding via GPR55 with nM potencies. Ligands such as cannabidiol and abnormal cannabidiol which exhibit no CB1 or CB2 activity and are believed to function at a novel cannabinoid receptor, also showed activity at GPR55. GPR55 couples to Galpha13 and can mediate activation of rhoA, cdc42 and rac1. CONCLUSIONS: These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB1 and CB2 described here will permit delineation of its physiological function(s).
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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 [31]
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- Authors
- Ryberg, E., Larsson, N., Sjögren, S., Hjorth, S., Hermansson, N., Leonova, J., Elebring, T., Nilsson, K., Drmota, T., & Greasley, P. J.
- Affiliations
- AstraZeneca (Sweden) (SE)
- Corresponding author
- Greasley, P J
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2007-12
- Volume
- 152
- Issue
- 7
- Pages
- 1092-1101
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC2095107
- OpenAlex
- W1819429514
- Cited by
- 1,568
- References
- 49
- Citations by year
- 2026: 36 · 2025: 65 · 2024: 70 · 2023: 79 · 2022: 112 · 2021: 126 · 2020: 123 · 2019: 96 · 2018: 91 · 2017: 82 · 2016: 76 · 2015: 71 · 2014: 76 · 2013: 71 · 2012: 77
- FWCI
- 52.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (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 › Neuroscience and Neuropharmacology Research
- Keywords
- GPR55, orphan receptors, cannabinoid receptors, endocannabinoid system, CP55,940, anandamide, cannabidiol, Gα13, G protein coupling, RhoA, Cdc42, Rac1, receptor signaling
- MeSH terms
- Amino Acid Sequence, Animals, Arachidonic Acids, Binding Sites, Binding, Competitive, Cannabidiol, Cannabinoids, Cell Line, Cloning, Molecular, Cyclohexanols, Humans, Ligands, Molecular Sequence Data, Organ Specificity, RNA, Messenger, Structure-Activity Relationship, Signal Transduction, Down-Regulation, Polymerase Chain Reaction, Guanosine 5'-O-(3-Thiotriphosphate), Receptors, G-Protein-Coupled, Receptors, Cannabinoid, Mice, Rats, Polyunsaturated Alkamides, Endocannabinoids
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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