Identification of WIN55212-3 as a competitive neutral antagonist of the human cannabinoid CB2 receptor.

TY - JOUR

T1 - Identification of WIN55212-3 as a competitive neutral antagonist of the human cannabinoid CB2 receptor.

AU - Savinainen, Juha R

AU - Kokkola, Tarja

AU - Salo, Outi M H

AU - Poso, Antti

AU - Järvinen, Tomi

AU - Laitinen, Jarmo T

PY - 2005

Y1 - 2005

N2 - 1. Several G protein-coupled receptors (GPCRs), including cannabinoid CB(1) and CB(2) receptors, show constitutive activity under heterologous expression. Such a tonic response is generated in the absence of an activating ligand, and can be inhibited by inverse agonists. Neutral antagonists, however, are silent at such receptors, but can reverse both agonist and inverse agonist responses. To date, no neutral antagonist for the CB(2) receptor has been reported. 2. Here, by monitoring receptor-dependent G protein activation, we demonstrate that WIN55212-3 acts as a neutral antagonist at the human CB(2) (hCB(2)) receptor. WIN55212-3 alone, at concentrations

AB - 1. Several G protein-coupled receptors (GPCRs), including cannabinoid CB(1) and CB(2) receptors, show constitutive activity under heterologous expression. Such a tonic response is generated in the absence of an activating ligand, and can be inhibited by inverse agonists. Neutral antagonists, however, are silent at such receptors, but can reverse both agonist and inverse agonist responses. To date, no neutral antagonist for the CB(2) receptor has been reported. 2. Here, by monitoring receptor-dependent G protein activation, we demonstrate that WIN55212-3 acts as a neutral antagonist at the human CB(2) (hCB(2)) receptor. WIN55212-3 alone, at concentrations

M3 - SCORING: Zeitschriftenaufsatz

VL - 145

SP - 636

EP - 645

JO - BRIT J PHARMACOL

JF - BRIT J PHARMACOL

SN - 0007-1188

IS - 5

M1 - 5

ER -