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Differential roles of CB1 and CB2 cannabinoid receptors in mast cells.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2003 May 15; Vol. 170 (10), pp. 4953-62. - Publication Year :
- 2003
-
Abstract
- Cannabinoid modulation of immune responses is a pathological consequence of marijuana abuse and a potential outcome of therapeutic application of the drug. Moreover, endogenous cannabinoids are physiological immune regulators. In the present report, we describe alterations in gene transcription that occur after cannabinoid exposure in a mast cell line, RBL2H3. Cannabinoid exposure causes marked changes in the transcript levels for numerous genes, acting both independently of and in concert with immunoreceptor stimulation via Fc epsilon RI. In two mast cell lines, we observed mRNA and protein expression corresponding to both CB1 and CB2 cannabinoid receptor isoforms, contrary to the prevailing view that CB1 is restricted to the CNS. We show that coexpression of the two isoforms is not functionally redundant in mast cells. Analysis of signaling pathways downstream of cannabinoid application reveals that activation of extracellular signal-regulated kinase, AKT, and a selected subset of AKT targets is accomplished by CB2 ligands and nonselective CB1/CB2 agonists in mast cells. CB1 inhibition does not affect AKT or extracellular signal-regulated kinase activation by cannabinoids, indicating that CB2 is the predominant regulatory receptor for these kinases in this cell context. CB1 receptors are, however, functional in these mast cells, since they can contribute to suppression of secretory responses.
- Subjects :
- Animals
Cannabinoids pharmacology
Cell Line
Cyclohexanols pharmacology
Enzyme Activation drug effects
Gene Expression Regulation drug effects
Immunosuppressive Agents pharmacology
Ligands
Mast Cells drug effects
Mast Cells enzymology
Mitogen-Activated Protein Kinases biosynthesis
Phosphorylation drug effects
Protein Isoforms biosynthesis
Protein Isoforms physiology
Proto-Oncogene Proteins biosynthesis
Proto-Oncogene Proteins c-akt
Rats
Receptors, Cannabinoid
Receptors, Drug biosynthesis
Receptors, Immunologic antagonists & inhibitors
Receptors, Immunologic physiology
Serotonin metabolism
Serotonin Antagonists pharmacology
Signal Transduction drug effects
Tumor Cells, Cultured
Cannabinoids metabolism
Mast Cells metabolism
Protein Serine-Threonine Kinases
Receptor, Cannabinoid, CB2
Receptors, Drug physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 170
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 12734338
- Full Text :
- https://doi.org/10.4049/jimmunol.170.10.4953