Cannabinoid Receptor 1 trafficking and the role of the intracellular pool: Implications for therapeutics

“Intracellular pool” CB1 receptors do not contribute to cell surface re-population, which requires new protein synthesis as CB1 does not recycle following internalization. Cannabinoid Receptor 1 (CB1), an abundant G-protein coupled receptor in the CNS, is currently of significant interest as a thera...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical pharmacology 2010-10, Vol.80 (7), p.1050-1062
Main Authors: Grimsey, Natasha L., Graham, E. Scott, Dragunow, Mike, Glass, Michelle
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cannabinoid Receptor CB1
Cannabinoids - metabolism
Cell Line
Cell Membrane - metabolism
Cell surface receptors
Cricetinae
Cytoplasm - metabolism
Downregulation
Endocytosis
Humans
Medical sciences
Pharmacology. Drug treatments
Protein trafficking
Protein Transport
Rats
Receptors, Cannabinoid - metabolism
Receptors, G-Protein-Coupled - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:“Intracellular pool” CB1 receptors do not contribute to cell surface re-population, which requires new protein synthesis as CB1 does not recycle following internalization. Cannabinoid Receptor 1 (CB1), an abundant G-protein coupled receptor in the CNS, is currently of significant interest as a therapeutic target. Although the cellular control of receptor trafficking is intimately linked with drug effects, CB1 trafficking is poorly defined in the current literature and conflicting evidence exists as to whether CB1 should be classified as a recycling, degrading or “dual-fate” receptor. Of particular interest is the widely noted intracellular pool which has been speculated to form part of a constitutive internalization and recycling pathway. This study performs a detailed quantification of CB1 trafficking in four cell lines, one of which expresses CB1 endogenously. We demonstrate that, contrary to previous reports, CB1 does not recycle following constitutive or agonist-induced internalization but instead exhibits a primarily degradative phenotype. Further, our data suggest that the intracellular pool does not contribute to cell surface re-population. These findings have significant implications for the interpretation of CB1 biochemical studies and the design and application of cannabinoid therapeutics.
ISSN:0006-2952
1873-2968
DOI:10.1016/j.bcp.2010.06.007