Binding properties of antagonists to Cannabinoid receptors in intact cells

Marie Wennerberg, L. Cheng, S. Hjorth, J.c. Clapham, A. Balendran, Georges Vauquelin

Onderzoeksoutput: Articlepeer review

13 Citaten (Scopus)


The implication of the cannabinoid receptor 1 (CB1 receptor) in several pathophysiological states has sparked the development of selective antagonists. Here we compare binding of the antagonists [3H]-AZ12491187, [3H]-taranabant and [3H]-rimonabant to intact human embryonic kidney cells stably expressing recombinant human CB1 receptors (CB1r cells). Unlabelled ligands decreased the total binding of the three radioligands with closely the same order of potency: i.e. AZ12288553 ? AZ12491187 ? taranabant > rimonabant. Non displaceable (i.e. non-specific) binding to the CB1r cells was the same as total binding to the wells containing untransfected cells and it was more pronounced for [3H]-AZ12491187 and [3H]-rimonabant than for [3H]-taranabant. [3H]-Rimonabant and (to a lesser extent) [3H]-AZ12491187 were also prone to bind non-specifically to the walls of the wells. Compared to the other radioligands, [3H]-rimonabant displayed lower potency for the CB1 receptors in saturation binding studies and faster association and dissociation in kinetic experiments. When dissociated, the three radioligands also showed prominent rebinding to the cells in medium only. This could be relieved by the presence of excess of unlabelled ligand and of bovine serum albumin (BSA) but a combination thereof was most efficient. The long `"residence time" of AZ12491187 at the CB1 receptor (due to slow dissociation and prominent rebinding) and its pronounced incorporation into the membranes of the cells could contribute to long-lasting in vivo CB1 receptor blockade.
Originele taal-2English
Pagina's (van-tot)200-210
Aantal pagina's11
TijdschriftFundamental and Clinical Pharmacology
Nummer van het tijdschrift2
StatusPublished - apr 2011


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