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 (hCB(1), hCB(1a), and hCB(1b),) 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 hCB(1) is the major transcript, and estimated that those of hCB(1a) and hCB(1b) 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-arachiclonoyl 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 hurnan cannabinoid CB1 receptor variants remains to be clarified. (C) 2008 Elsevier B.V. All rights reserved.