International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2

By R. Pertwee, Allyn C. Howlett, M. Abood, Stephen P. H. Alexander, V. Di Marzo, M. Elphick, P. Greasley, H. Hansen, George Kunos, K. Mackie and 2 more. Pharmacological Reviews, 2010

1,739 citations recorded by the source corpus.

There are at least two types of cannabinoid receptors (CB1 and CB2). Ligands activating these G protein-coupled receptors (GPCRs) include the phytocannabinoid Δ9-tetrahydrocannabinol, numerous synthetic compounds, and endogenous compounds known as endocannabinoids. Cannabinoid receptor antagonists have also been developed. Some of these ligands activate or block one type of cannabinoid receptor more potently than the other type. This review summarizes current data indicating the extent to which cannabinoid receptor ligands undergo orthosteric or allosteric interactions with non-CB1, non-CB2 established GPCRs, deorphanized receptors such as GPR55, ligand-gated ion channels, transient receptor potential (TRP) channels, and other ion channels or peroxisome proliferator-activated nuclear receptors. From these data, it is clear that some ligands that interact similarly with CB1 and/or CB2 receptors are likely to display significantly different pharmacological profiles. The review also lists some criteria that any novel “CB3” cannabinoid receptor or channel should fulfil and concludes that these criteria are not currently met by any non-CB1, non-CB2 pharmacological receptor or channel. However, it does identify certain pharmacological targets that should be investigated further as potential CB3 receptors or channels. These include TRP vanilloid 1, which possibly functions as an ionotropic cannabinoid receptor under physiological and/or pathological conditions, and some deorphanized GPCRs. Also discussed are 1) the ability of CB1 receptors to form heteromeric complexes with certain other GPCRs, 2) phylogenetic relationships that exist between CB1/CB2 receptors and other GPCRs, 3) evidence for the existence of several as-yet-uncharacterized non-CB1, non-CB2 cannabinoid receptors; and 4) current cannabinoid receptor nomenclature.

Subfields: Cellular and Molecular Neuroscience, Endocrinology, Diabetes and Metabolism, Pharmacology

View Paper: https://www.semanticscholar.org/paper/bc19f6b7524d32154217fa1b4c74c727ed3a4fba

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In Cellular and Molecular Neuroscience

1. L. Parker
2. P. Castillo
3. Y. Hashimotodani
4. R. Mechoulam
5. R. Malenka

In Pharmacology

1. L. Parker
2. P. Castillo
3. Y. Hashimotodani
4. R. Mechoulam

Citations in the corpus

• The endocannabinoid system and the brain. (2013, background): “This may be due to the ability of CB1 receptors to form heteromeric complexes with other GPCRs (Pertwee et al. 2010).”
• Endocannabinoid signaling and synaptic function (2012, methodology): “While other effectors downstream of CB 1 Rs have been described, mainly in cultured cells and expression systems (Howlett, 2005; Pertwee et al., 2010), their role in regulating synaptic function is presently less clear.”