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This work was supported in part by NIDA/IRP and ESO acknowledges the technical assistance and financial support from William Paterson University Center for Research, Biology department, the Dean's ( Dr De Young) student worker fund, and the Provost office for assigned release time. The CB2 knockout and their wild- type control mice were developed by Buckley et al. ( 2000), and obtained from NIAAA through Dr Kunos. Part of human brain tissue was obtained from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, Maryland. The authors would also like to acknowledge the technical assistance of Dr Xia Li from Chemical Biology Research Branch and English editing by Dr Mary Pfeiffer, Editor and Writer NIDA, IRP. ALB and MPV acknowledges Red de Trastornos Adictivos (RD06/0001/1013). We thank Dr John McPartland for his excellent and in-depth review of the manuscript and for his suggestions.

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Species differences in cannabinoid receptor 2 (CNR2 gene): identification of novel human and rodent CB2 isoforms, differential tissue expression and regulation by cannabinoid receptor ligands

Publicado en:GENES BRAIN AND BEHAVIOR. 8 (5): 519-530 - 2009-07-01 8(5), DOI: 10.1111/j.1601-183X.2009.00498.x

Autores: Liu, Q. -R.; Pan, C. -H.; Hishimoto, A.; Li, C. -Y.; Xi, Z. -X.; Llorente-Berzal, A.; Viveros, M. -P.; Ishiguro, H.; Arinami, T.; Onaivi, E. S.; Uhl, G. R.;

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Cannabinoids, endocannabinoids and marijuana activate two well-characterized cannabinoid receptors (CB-Rs), CB1-Rs and CB2-Rs. The expression of CB1-Rs in the brain and periphery has been well studied, but neuronal CB2-Rs have received much less attention than CB1-Rs. Many studies have now identified and characterized functional glial and neuronal CB2-Rs in the central nervous system. However, many features of CB2-R gene structure, regulation and variation remain poorly characterized in comparison with the CB1-R. In this study, we report on the discovery of a novel human CB2 gene promoter transcribing testis (CB2A) isoform with starting exon located ca 45 kb upstream from the previously identified promoter transcribing the spleen isoform (CB2B). The 5' exons of both CB2 isoforms are untranslated 5'UTRs and alternatively spliced to the major protein coding exon of the CB2 gene. CB2A is expressed higher in testis and brain than CB2B that is expressed higher in other peripheral tissues than CB2A. Species comparison found that the CB2 gene of human, rat and mouse genomes deviated in their gene structures and isoform expression patterns. mCB2A expression was increased significantly in the cerebellum of mice treated with the CB-R mixed agonist, WIN55212-2. These results provide much improved information about CB2 gene structure and its human and rodent variants that should be considered in developing CB2-R-based therapeutic agents.

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