Similar in vitro pharmacology of human cannabinoid CB1 receptor variants expressed in CHO cells

Through alternative splicing, the human cannabinoid CB1 receptor gene encodes three variants of protein products (hCB1, hCB1a, and hCB1b) that differ in amino acid sequence at the N terminus of the receptors. By semi-quantitative PCR from human adult and fetal brain mRNA, we demonstrated that the transcript encoding hCB1 is the major transcript, and estimated that those of hCB1a and hCB1b represent fewer than 5% of the total human cannabinoid CB1 receptor transcripts. We characterized the three variants stably expressed in CHO cells. In the contrary to the study by Ryberg et al. (FEBS Lett 579[1], 259-64), we did not find substantial difference among the three variants according to the binding affinity, functional potency, and efficacy of meth-anandamide, 2-arachidonoyl glycerol, virodhamine, Noladin ether, docosatetraenylethanolamide, CP55940, AM251, and compound 35e (an acyclic class human CB1 receptor inverse agonist similar to MK-0364). The functional significance of different human cannabinoid CB1 receptor variants remains to be clarified.