Distribution, Dimerization and Function of Human Cannabinoid Receptor Type 1 Coding Region Splice Variants

Abstract

The pharmacological functions of the type 1 human cannabinoid receptor (hCB1) are thought to be modulated through the isoform encoded by the fourth exon of the CNR1 gene. Two other mRNA variants of the coding region of this receptor have been described, hCB1a and hCB1b. The contribution of these variants to endocannabinoid physiology and pharmacology remains unclear. In the present study, the three hCB1 coding region variants mRNAs were detected in all human brain regions examined. Western blot analysis of homogenates from different regions of the monkey brain demonstrated that proteins with the expected molecular weights of CB1, CB1a and CB1b receptors are present throughout the brain. In HEK cells, each of the receptor variants could form homodimers and variants formed heterodimers. Heterodimerization affected both the trafficking of hCB1 receptor complexes and signalling in response to cannabinoid agonists.