Anti-CNR1 monoclonal antibody, clone 3G0

Dopamine D-2 receptors are the main target of antipsychotic drugs. In the brain, D-2 receptors coexpress with adenosine A(2A) and CB1 cannabinoid receptors, leading to functional interactions. The protein and messenger RNA (mRNA) contents of A(2A), D-2, and CB1 receptors were quantified in postmortem prefrontal cortex of subjects with schizophrenia. The study was performed in subjects suffering schizophrenia (n = 31) who mainly died by suicide, matched with non-schizophrenia suicide victims (n = 13) and non-suicide controls (n = 33). The density of receptor proteins was evaluated by immunodetection techniques, and their relative mRNA expression was quantified by quantitative real-time polymerase chain reaction. In schizophrenia, the densities of A(2A) (90 +/- 6%, n = 24) and D-2-like receptors (95 +/- 5%, n = 22) did not differ from those in controls (100%). Antipsychotic treatment did not induce changes in the protein expression. In contrast, the immunodensity of CB1 receptors was significantly decreased (71 +/- 7%, n = 11; p < 0.05) in antipsychotic-treated subjects with schizophrenia but not in drug-free subjects (104 +/- 13%, n = 11). The relative mRNA amounts encoding for A(2A), D-2, and CB1 receptors were similar in brains of drug-free, antipsychotic-treated subjects with schizophrenia and controls. The findings suggest that antipsychotics induce down-regulation of CB1 receptors in brain. Since A(2A), D-2, and CB1 receptors coexpress on brain GABAergic neurons and reductions in markers of GABA neurotransmission have been identified in schizophrenia, a lower density of CB1 receptor induced by antipsychotics could represent an adaptative mechanism that reduces the endocannabinoid-mediated suppression of GABA release, contributing to the normalization of cognitive functions in the disorder.

The endocannabinoid system (ECS) plays a key role in the regulation of appetite, body weight and metabolism. We undertook the present study to further clarify the regulation of the cannabinoid CB1 receptor (CB1, CNR1) in human adipose tissue in obesity. CB1 receptor mRNA expression was similar to 1.6-fold (P<0.004) and 1.9-fold higher (P<0.05) in subcutaneous adipocytes from obese compared to non-obese subjects in microarray and quantitative real-time PCR studies, respectively. Higher CB1 receptor mRNA expression levels in both adipose tissue (similar to 1.2 fold, P<0.05) and adipocytes (similar to 2 fold, P<0.01) were observed in samples from visceral compared to subcutaneous depots collected from 22 obese individuals. Immunofluorescence confocal microscopy demonstrated the presence of CB1 receptor on adipocytes and also adipose tissue macrophages. These data indicate that adipocyte CB1 receptor is up-regulated in human obesity and visceral adipose tissue and also suggest a potential role for the ECS in modulating immune/inflammation as well as fat metabolism in adipose tissue.