μ-Opioid Receptor Internalization: Opiate Drugs Have Differential Effects on a Conserved Endocytic Mechanism In Vitro and in the Mammalian Brain

1998 ◽  
Vol 53 (3) ◽  
pp. 377-384 ◽  
Author(s):  
Duane E. Keith ◽  
Benito Anton ◽  
Stephen R. Murray ◽  
Paulette A. Zaki ◽  
Peter C. Chu ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Internalization ◽  
Mammalian Brain ◽  
Differential Effects ◽  
Opiate Drugs ◽  
Μ Opioid Receptor

Differential effects of morphine and cocaine on locomotor activity and sensitization in μ-opioid receptor knockout mice

2003 ◽  
Vol 344 (1) ◽  
pp. 37-40 ◽  
Author(s):  
Ji-Hoon Yoo ◽  
Eun-Mi Yang ◽  
Seok-Yong Lee ◽  
Horace H. Loh ◽  
Ing K. Ho ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Opioid Receptor ◽  
Knockout Mice ◽  
Differential Effects ◽  
Μ Opioid Receptor

scholarly journals Dexamethasone-induced selective inhibition of the central μ opioid receptor: functional in vivo and in vitro evidence in rodents

1994 ◽  
Vol 113 (4) ◽  
pp. 1416-1422 ◽  
Author(s):  
S. Pieretti ◽  
A. Giannuario ◽  
M.R. Domenici ◽  
S. Sagratella ◽  
A. Capasso ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Selective Inhibition ◽  
Μ Opioid Receptor

Differential effects of morphine, DPDPE, and U-50488 on apomorphine-induced climbing behavior in μ-opioid receptor knockout mice

2001 ◽  
Vol 94 (1-2) ◽  
pp. 197-199 ◽  
Author(s):  
Choon-Gon Jang ◽  
Seok-Yong Lee ◽  
Younjoo Park ◽  
Tangeng Ma ◽  
Horace H Loh ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Knockout Mice ◽  
Differential Effects ◽  
Climbing Behavior ◽  
Μ Opioid Receptor

scholarly journals In vivo and in vitro inhibition of human liver cancer progress by downregulation of the μ-opioid receptor and relevant mechanisms

2013 ◽  
Vol 30 (4) ◽  
pp. 1731-1738 ◽  
Author(s):  
JIN LU ◽  
ZEFENG LIU ◽  
LINGLING ZHAO ◽  
HUIMIN TIAN ◽  
XIUHUA LIU ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Opioid Receptor ◽  
Human Liver ◽  
Human Liver Cancer ◽  
Μ Opioid Receptor ◽  
In Vitro Inhibition

scholarly journals Dissecting the roles of GRK2 and GRK3 in μ-opioid receptor internalization and β-arrestin2 recruitment using CRISPR/Cas9-edited HEK293 cells

2020 ◽  
Author(s):  
Thor C. Møller ◽  
Mie F. Pedersen ◽  
Jeffrey R. van Senten ◽  
Sofie D. Seiersen ◽  
Jesper M. Mathiesen ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
G Protein Coupled Receptors ◽  
Receptor Internalization ◽  
Hek293 Cells ◽  
Molecule Inhibitor ◽  
Wide Range ◽  
Individual Contributions ◽  
Μ Opioid Receptor ◽  
G Protein Coupled ◽  
Target Effects

AbstractMost G protein-coupled receptors (GPCRs) recruit β-arrestins and internalize upon agonist stimulation. For the μ-opioid receptor (μ-OR), this process has been linked to development of opioid tolerance. GPCR kinases (GRKs), particularly GRK2 and GRK3, have been shown to be important for μ-OR recruitment of β-arrestin and internalization. However, the contribution of GRK2 and GRK3 to β-arrestin recruitment and receptor internalization, remain to be determined in their complete absence. Using CRISPR/Cas9-mediated genome editing we established HEK293 cells with knockout of GRK2, GRK3 or both to dissect their individual contributions in β-arrestin2 recruitment and μ-OR internalization upon stimulation with four different agonists. We showed that GRK2/3 removal reduced agonist-induced μ-OR internalization and β-arrestin2 recruitment substantially and we found GRK2 to be more important for these processes than GRK3. Furthermore, we observed a sustained and GRK2/3 independent component of β-arrestin2 recruitment to the plasma membrane upon μ-OR activation. Rescue expression experiments restored GRK2/3 functions. Inhibition of GRK2/3 using the small molecule inhibitor CMPD101 showed a high similarity between the genetic and pharmacological approaches, cross-validating the specificity of both. However, off-target effects were observed at high CMPD101 concentrations. These GRK2/3 KO cell lines should prove useful for a wide range of studies on GPCR function.

scholarly journals Dissecting the roles of GRK2 and GRK3 in μ-opioid receptor internalization and β-arrestin2 recruitment using CRISPR/Cas9-edited HEK293 cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Thor C. Møller ◽  
Mie F. Pedersen ◽  
Jeffrey R. van Senten ◽  
Sofie D. Seiersen ◽  
Jesper M. Mathiesen ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
G Protein Coupled Receptors ◽  
Receptor Internalization ◽  
Hek293 Cells ◽  
Molecule Inhibitor ◽  
Wide Range ◽  
Individual Contributions ◽  
Μ Opioid Receptor ◽  
G Protein Coupled ◽  
Target Effects

Abstract Most G protein-coupled receptors (GPCRs) recruit β-arrestins and internalize upon agonist stimulation. For the μ-opioid receptor (μ-OR), this process has been linked to development of opioid tolerance. GPCR kinases (GRKs), particularly GRK2 and GRK3, have been shown to be important for μ-OR recruitment of β-arrestin and internalization. However, the contribution of GRK2 and GRK3 to β-arrestin recruitment and receptor internalization, remain to be determined in their complete absence. Using CRISPR/Cas9-mediated genome editing we established HEK293 cells with knockout of GRK2, GRK3 or both to dissect their individual contributions in β-arrestin2 recruitment and μ-OR internalization upon stimulation with four different agonists. We showed that GRK2/3 removal reduced agonist-induced μ-OR internalization and β-arrestin2 recruitment substantially and we found GRK2 to be more important for these processes than GRK3. Furthermore, we observed a sustained and GRK2/3 independent component of β-arrestin2 recruitment to the plasma membrane upon μ-OR activation. Rescue expression experiments restored GRK2/3 functions. Inhibition of GRK2/3 using the small molecule inhibitor CMPD101 showed a high similarity between the genetic and pharmacological approaches, cross-validating the specificity of both. However, off-target effects were observed at high CMPD101 concentrations. These GRK2/3 KO cell lines should prove useful for a wide range of studies on GPCR function.

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