The human type 1 cannabinoid (hCB₁) receptor is expressed at high levels in the central nervous system. mRNA variants of the coding region of this receptor, human cannabinoid hCB_1a and hCB_1b receptors, have been identified, their biological function remains unclear. The present study demonstrated that the three human cannabinoid hCB₁ coding region variants are expressed in the human and monkey (Macaca fascicularis) brain. Western blot analyses of homogenates from different regions of the monkey brain demonstrated that proteins with the expected molecular weights of the cannabinoid CB₁, CB_1a and CB_1b receptors were co-expressed throughout the brain. Given the co-localization of these receptors, we hypothesized that physical interactions between the three splice variants may affect cannabinoid pharmacology. The human cannabinoid hCB₁, hCB_1a, and hCB_1b receptors formed homodimers and heterodimers, as determined by BRET in transiently transfected HEK 293A cells. We found that the co-expression of the human cannabinoid hCB₁ and each of the splice variants increased cell surface expression of the human cannabinoidhCB₁ receptor and increased G_i/o-dependent ERK phosphorylation in response to cannabinoid agonists. Therefore, the human cannabinoid hCB₁coding region splice variants play an important physiological role in the activity of the endocannabinoid system.
© 2013 Published by Elsevier B.V.

PMID:

 

24091169

 

[PubMed – as supplied by publisher]