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

Xiao J.C., Jewell J.P., Lin L.S., Hagmann W.K., Fong T.M., Shen C.P.

Through alternative splicing, the human cannabinoid CB(1) 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 CB(1) 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 CB(1) receptor inverse agonist similar to MK-0364). The functional significance of different human cannabinoid CB(1) receptor variants remains to be clarified.

Brain Res. 1238:36-43(2008) [PubMed] [Europe PMC]

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