Despite the profound effect of cannabinoids on motor function, and their therapeutic potential in Parkinson's and Huntington's diseases, the cellular and subcellular distributions of striatal CB1 receptors are not well defined. Here, we show that CB1 receptors are primarily located on GABAergic (vesicular GABA transporter-positive) and glutamatergic [vesicular glutamate transporter-1 (VGLUT-1)-...

Human cannabinoid type 1 (CB1) G-protein coupled receptor is a potential therapeutic target for obesity. The previously predicted and experimentally validated ensemble of ligand-free conformations of CB1 [Scott, C. E. et al. Protein Sci. 2013 , 22 , 101 - 113 ; Ahn, K. H. et al. Proteins 2013 , 81 , 1304 - 1317] are used here to predict the binding sites for known CB1-selective inverse agonists...

It is widely accepted that cannabinoids regulate GABA release by activation of cannabinoid receptor type 1 (CB1). Results obtained from a variety of brain regions consistently indicate that cannabinoid agonists can also reduce glutamatergic synaptic transmission. However, there are still conflicting data concerning the role of CB1 in cannabinoid-induced inhibition of glutamatergic transmission ...

The endocannabinoid system affects the neuroendocrine regulation of hormone secretion, including the activity of the hypothalamus-pituitary-adrenal (HPA) axis. However, the mechanisms by which endocannabinoids regulate HPA axis function have remained unclear. Here we demonstrate that mice lacking cannabinoid receptor type 1 (CB1-/-) display a significant dysregulation of the HPA axis. Although ...

The recent discovery of allosteric modulators of the CB1 receptor including PSNCBAM-1 (4) has generated significant interest in CB1 receptor allosteric modulation. Here in the first SAR study on 4, we have designed and synthesized a series of analogs focusing on modifications at two positions. Pharmacological evaluation in calcium mobilization and binding assays revealed the importance of alkyl...

CB1 cannabinoid (CB1) and D2 dopamine (D2) receptors are known to couple to the G protein G i/o. It has been reported that concurrent activation of D2 receptors and CB1 receptors, in primary striatal neuronal culture, promotes functional CB1 receptor coupling to G s resulting in elevations in intracellular cyclic AMP levels. We now report that in the absence of D2 receptors, acute activation of...

The primary aim of the present study was to determine the expression levels of cannabinoid receptor type 1 (CB1) in steatotic rat livers. The secondary aim was to clarify whether steatosis and inflammation are more marked in areas with increased CB1 overexpression. For ethical and economic reasons, the present study investigated tissue from archived liver blocks, which were obtained from 38 rat...

gp57/42 is a membrane glycoprotein localized in the trans-Golgi, flagellar pocket region of the cell surface, endosomes and lysosomes of bloodstream forms of Trypanosoma brucei rhodesiense. Pulse-chase immunoprecipitation experiments revealed that gp57/42 acquires a unique N-linked oligosaccharide recognized by the CB1 monoclonal antibody 20-30 minutes after protein synthesis, probably in the t...

The intestinal hormone cholecystokinin (CCK) inhibits food intake via stimulation of vagal afferent neurons (VAN). Recent studies suggest that CCK also regulates the expression of some G protein-coupled receptors and neuropeptide transmitters in these neurons. The aim of the present study was to characterize the expression of cannabinoid (CB)1 receptors in VAN and to determine whether stimulati...

Cannabinoid receptors type 1 (CB1) play a central role in both short-term and long-term extinction of auditory-cued fear memory. The molecular mechanisms underlying this function remain to be clarified. Several studies indicated extracellular signal-regulated kinases (ERKs), the phosphatidylinositol 3-kinase with its downstream effector AKT, and the phosphatase calcineurin as potential molecula...