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• W1890012419 abstract "Agonist-induced internalization of G-protein-coupled receptors is an important mechanism for regulating receptor abundance and availability at the plasma membrane. In this study we have used immunolabeling techniques and confocal microscopy to investigate agonist-induced internalization and trafficking of CB₁receptors in rat cultured hippocampal neurons. The levels of cell surface CB₁ receptor immunoreactivity associated with presynaptic GABAergic terminals decreased markedly (by up to 84%) after exposure to the cannabinoid agonist (+)-WIN55212, in a concentration-dependent (0.1–1 μm) and stereoselective manner. Inhibition was maximal at 16 hr and abolished in the presence of SR141716A, a selective CB₁ receptor antagonist. Methanandamide (an analog of an endogenous cannabinoid, anandamide) also reduced cell surface labeling (by 43% at 1 μm). Differential labeling of cell surface and intracellular pools of receptor demonstrated that the reduction in cell surface immunoreactivity reflects agonist-induced internalization and suggests that the internalized CB₁ receptors are translocated toward the soma. The internalization process did not require activated G-protein α(i) or α(o) subunits. A different pattern of cell surface CB₁ receptor expression was observed using an undifferentiated F-11 cell line, which had pronounced somatic labeling. In these cells substantial CB₁ receptor internalization was also observed after exposure to (+)-WIN55212 (1 μm) for relatively short periods (30 min) of agonist exposure. In summary, this dynamic modulation of CB₁ receptor expression may play an important role in the development of cannabinoid tolerance in the CNS. Agonist-induced internalization at presynaptic terminals has important implications for the modulatory effects of G-protein-coupled receptors on neurotransmitter release." @default.
• W1890012419 created "2016-06-24" @default.
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• W1890012419 date "2001-04-01" @default.
• W1890012419 modified "2023-10-18" @default.
• W1890012419 title "Agonist-Induced Internalization and Trafficking of Cannabinoid CB₁Receptors in Hippocampal Neurons" @default.
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• W1890012419 doi "https://doi.org/10.1523/jneurosci.21-07-02425.2001" @default.
• W1890012419 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6762401" @default.
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