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Page 1 de 36 résultats
Mutation of putative GRK phosphorylation sites in the cannabinoid receptor 1 (CB1R) confers resistance to cannabinoid tolerance and hypersensitivity to cannabinoids in mice.
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For many G-protein-coupled receptors (GPCRs), including cannabinoid receptor 1 (CB1R), desensitization has been proposed as a principal mechanism driving initial tolerance to agonists. GPCR desensitization typically requires phosphorylation by a G-protein-coupled receptor kinase (GRK) and
Functional roles of the tyrosine within the NP(X)(n)Y motif and the cysteines in the C-terminal juxtamembrane region of the CB2 cannabinoid receptor.
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In G protein-coupled receptors, a NP(X)(n)Y motif in the seventh transmembrane domain and cysteine residues in the C-terminal juxtamembrane region are conserved. In the current study, the roles of Y299 within the NPVIY motif and C313 and C320 in the C-terminal juxtamembrane region of the human CB2
F200A substitution in the third transmembrane helix of human cannabinoid CB1 receptor converts AM2233 from receptor agonist to inverse agonist.
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To investigate how specific amino acid residues affect human cannabinoid CB1 receptor binding and activation, CHO cell lines stably expressing wild type and the phenylalanine 200 to alanine mutant of human cannabinoid CB1 receptor (F200A) were examined. AM2233 functions as an agonist at the wild
The second intracellular loop of the human cannabinoid CB2 receptor governs G protein coupling in coordination with the carboxyl terminal domain.
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The major effects of cannabinoids and endocannabinoids are mediated via two G protein-coupled receptors, CB1 and CB2, elucidation of the mechanism and structural determinants of the CB2 receptor coupling with G proteins will have a significant impact on drug discovery. In the present study, we
Functional role of serine residues of transmembrane dopamin VII in signal transduction of CB2 cannabinoid receptor.
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Using site-directed mutagenesis technique, I have replaced serine 285 and serine 292 with the alanine, and assessed the binding of agonist and signaling such as the inhibition of adenylyl cyclase activity. I have found that serine 292 has an important role in the signal transduction of cannabinoid
Mutational analysis and molecular modelling of the antagonist SR 144528 binding site on the human cannabinoid CB(2) receptor.
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We have investigated the binding site of the subtype specific antagonist SR 144528, (N-[(1S)-endo-1,3,3-trimethyl bicyclo [2.2. 1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methoxybenzyl)- pyrazo le-3-carboxamide) on the human cannabinoid CB(2) receptor based on functional studies with mutated
Integrity of extracellular loop 1 of the human cannabinoid receptor 1 is critical for high-affinity binding of the ligand CP 55,940 but not SR 141716A.
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Like other G-protein coupled receptors with hydrophobic ligands, the human cannabinoid receptor 1 (CB1) is thought to bind its ligands within the transmembrane region of the receptor. However, for some of these receptors the extracellular loops (ECs) have also been shown to play a role in ligand
A common molecular basis for exogenous and endogenous cannabinoid potentiation of glycine receptors.
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Both exogenous and endogenous cannabinoids can allosterically modulate glycine receptors (GlyRs). However, little is known about the molecular basis of cannabinoid-GlyR interactions. Here we report that sustained incubation with the endocannabinoid anandamide (AEA) substantially increased the
Hydrophobic residues in helix 8 of cannabinoid receptor 1 are critical for structural and functional properties.
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In addition to the heptahelical transmembrane domain shared by all G protein-coupled receptors (GPCRs), many class A GPCRs adopt a helical domain, termed helix 8, in the membrane-proximal region of the C terminus. We investigated the role of residues in the hydrophobic and hydrophilic faces of
Modulation of the cannabinoid receptors by andrographolide attenuates hepatic apoptosis following bile duct ligation in rats with fibrosis.
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Bile acid-induced apoptosis plays an important role in the pathogenesis of cholestatic liver disease, and its prevention is of therapeutic interest. The aim of this study was to test whether the andrographolide limits the evolution of apoptosis in a murine model of bile duct ligation (BDL)-induced
[Cannabinoid receptor 2 deletion promotes proliferation and activation of hepatic macrophages in mice with acute liver injury induced by concanavalin A].
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Objective To investigate the effect of cannabinoid receptor 2 (CB2) gene deletion on liver macrophages in mice with acute liver injury induced by concanavalin A (ConA). Methods The mice with gene deletion were identified by PCR. Twenty 8-week-old wild-type C57BL/6J male mice were randomly divided
Dual role of the second extracellular loop of the cannabinoid receptor 1: ligand binding and receptor localization.
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The seven transmembrane alpha-helices of G protein-coupled receptors (GPCRs) are the hallmark of this superfamily. Intrahelical interactions are critical to receptor assembly and, for the GPCR subclass that binds small molecules, ligand binding. Most research has focused on identifying the ligand
Novel insights into CB1 cannabinoid receptor signaling: a key interaction identified between the extracellular-3 loop and transmembrane helix 2.
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Activation of the cannabinoid CB1 receptor (CB1) is modulated by aspartate residue D2.63(176) in transmembrane helix (TMH) 2. Interestingly, D2.63 does not affect the affinity for ligand binding at the CB1 receptor. Studies in class A G protein-coupled receptors have suggested an ionic interaction
The CB1 cannabinoid receptor C-terminus regulates receptor desensitization in autaptic hippocampal neurones.
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OBJECTIVE
The cannabinoid CB(1) receptor is the chief mediator of the CNS effects of cannabinoids. In cell culture model systems, CB(1) receptors both desensitize and internalize on activation. Previous work suggests that the extreme carboxy-terminus of this receptor regulates internalization via
An aromatic microdomain at the cannabinoid CB(1) receptor constitutes an agonist/inverse agonist binding region.
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The cannabinoid CB(1) receptor transmembrane helix (TMH) 3-4-5-6 region includes an aromatic microdomain comprised of residues F3.25, F3.36, W4.64, Y5.39, W5.43, and W6.48. In previous work, we have demonstrated that aromaticity at position 5.39 in CB(1) is crucial for proper function of CB(1).
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