Trends in Pharmacological Sciences
ReviewCannabinoid CB2 receptor: a new target for controlling neural cell survival?
Section snippets
Introduction: the cannabinoid signaling system
The great increase in cannabinoid research in recent years has been a direct consequence of the discovery of the ‘endogenous cannabinoid system’ – a new intercellular communication network [1]. The endogenous cannabinoid system comprises at least two types of G protein-coupled receptor, called the cannabinoid CB1 and CB2 receptors, that are activated by a family of endogenous arachidonic acid derivatives, the endocannabinoids, and by Δ9-tetrahydrocannabinol (Δ9-THC), the principal active
Biochemistry, pharmacology and distribution of the CB2 receptor
The gene encoding the human cannabinoid CB2 receptor was cloned in 1993 (recently reviewed in Ref. [8]). It is located in chromosome 1p36 and encodes a protein of 360 amino acids with an overall homology to CB1 receptors of 44%, although this homology rises to 68% when only the transmembrane regions are compared. It belongs to the seven-transmembrane-domain, G-protein-coupled receptor class [9], and can modulate various signal transduction pathways involved in controlling cell proliferation,
The CB2 receptor and the cell death or survival decision
The CB2 receptor has been implicated in controlling the proliferation, differentiation and survival of both neural and non-neural cells. For example, activation of CB2 receptors in rat RTMGL1 microglial cells [11] and mouse neural progenitors [12] promotes cell proliferation. Moreover, an inverse relation between expression of the CB2 receptor and the stage of cell differentiation is evident in neural cells (from neural progenitors to mature neurons and neuroglial cells [12]) and in B cells
Concluding remarks and future perspectives
Recent data support the concept that brain CB2 receptors have important functions in attenuating neuroinflammatory processes and in inhibiting the survival of transformed neural cells. These receptors are upregulated in pathological conditions, presumably as part of an endogenous mechanism of defense against various brain-damaging insults; however, further work is required to obtain full characterization of the possible roles that these receptors have in those processes.
Essential issues to be
Acknowledgements
We thank our laboratory colleagues for continuous support. Work in our laboratories is funded by grants from the Ministerio de Educación y Ciencia (SAF2006–11333 to J.F-R., SAF2004–00237 to J.R., SAF2006–00918 to M.G.), Fundación Científica de la Asociación Española Contra el Cáncer (to M.G.), Universidad Complutense-Comunidad de Madrid (950344 to M.G. and J.F-R.) and Fundación Mapfre Medicina (to J.R.).
References (60)
Cannabinoids and cell fate
Pharmacol. Ther.
(2002)The endogenous cannabinoid system and the basal ganglia. biochemical, pharmacological, and therapeutic aspects
Pharmacol. Ther.
(2002)Echinacea alkylamides modulate TNF-α gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways
FEBS Lett.
(2004)p38 MAPK is involved in CB2 receptor-induced apoptosis of human leukaemia cells
FEBS Lett.
(2005)The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells
Cancer Cell
(2006)Biochemistry, pharmacology and physiology of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand
Prog. Lipid Res.
(2006)- et al.
A historical overview of chemical research on cannabinoids
Chem. Phys. Lipids
(2000) The endocannabinoid anandamide protects neurons during CNS inflammation by induction of MKP-1 in microglial cells
Neuron
(2006)Actions of cannabinoid receptor ligands on rat cultured sensory neurones: implications for antinociception
Neuropharmacology
(2001)Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin
J. Dermatol. Sci.
(2005)
Peripheral nerve injury induces cannabinoid receptor 2 protein expression in rat sensory neurons
Neuroscience
Modulation and functional involvement of CB2 peripheral cannabinoid receptors during B-cell differentiation
Blood
The peripheral cannabinoid receptor CB2, frequently expressed on AML blasts, either induces a neutrophilic differentiation block or confers abnormal migration properties in a ligand-dependent manner
Blood
Cannabinoids and brain injury: therapeutic implications
Trends Mol. Med.
Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: relevance to Parkinson's disease
Neurobiol. Dis.
AM1241, a cannabinoid CB2 receptor selective compound, delays disease progression in a mouse model of amyotrophic lateral sclerosis
Eur. J. Pharmacol.
Hypothesis: cannabinoid therapy for the treatment of gliomas?
Neuropharmacology
The molecular logic of endocannabinoid signalling
Nat. Rev. Neurosci.
Cannabinoid receptors as therapeutic targets
Annu. Rev. Pharmacol. Toxicol.
Cannabinoids: potential anticancer agents
Nat. Rev. Cancer
Pharmacological actions of cannabinoids
Handb. Exp. Pharmacol.
Cannabinoids in neurodegeneration and neuroprotection
Targeting the cannabinoid CB2 receptor: mutations, modeling and development of CB2 selective ligands
Curr. Med. Chem.
International Union of Pharmacology. XXVII. Classification of cannabinoid receptors
Pharmacol. Rev.
Signaling pathway associated with stimulation of CB2 peripheral cannabinoid receptor. Involvement of both mitogen-activated protein kinase and induction of Krox-24 expression
Eur. J. Biochem.
Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism
Mol. Pharmacol.
Non-psychoactive CB2 cannabinoid agonists stimulate neural progenitor proliferation
FASEB J.
Cannabinoids promote oligodendrocyte progenitor survival: involvement of cannabinoid receptors and phosphatidylinositol 3-kinase/Akt signaling
J. Neurosci.
Differential roles of CB1 and CB2 cannabinoid receptors in mast cells
J. Immunol.
Inhibition of glioma growth in vivo by selective activation of the CB2 cannabinoid receptor
Cancer Res.
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