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

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)519-530
Number of pages12
JournalGenes, Brain and Behavior
Volume8
Issue number5
DOIs
StatePublished - Jul 2009
Externally publishedYes

Fingerprint

Cannabinoid Receptors
Forensic Anthropology
Rodentia
Protein Isoforms
Ligands
Exons
Genes
Testis
Cannabinoid Receptor CB2
vpr Genes
Cannabinoid Receptor CB1
Endocannabinoids
Cannabinoids
Brain
Cannabis
Neuroglia
Cerebellum
Spleen
Central Nervous System
Genome

Keywords

  • Brain
  • CB2 cannabinoid receptors
  • CB2A
  • CB2B
  • Spleen
  • Testis

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology

Cite this

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. / 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.

In: Genes, Brain and Behavior, Vol. 8, No. 5, 07.2009, p. 519-530.

Research output: Contribution to journalArticle

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. / 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. In: Genes, Brain and Behavior. 2009 ; Vol. 8, No. 5. pp. 519-530.
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AU - Llorente-Berzal, A.

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