 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, July 1, 2002, 22(13):5769-5776
µ-Opioid Receptors: Ligand-Dependent Activation of Potassium Conductance, Desensitization, and Internalization
Veronica A. Alvarez1, *, Seksiri Arttamangkul2, *, Vu Dang1, 2, Abdallah Salem1, 3, Jennifer L. Whistler4, Mark von Zastrow5, David K. Grandy2, and John T. Williams1 1 Vollum Institute and 2 Department of Physiology and Pharmacology, Oregon Health and Sciences University, Portland, Oregon 97201, 3 Department of Clinical and Experimental Pharmacology, Adelaide University, Adelaide SA 5005, Australia, 4 Ernest Gallo Clinic and Research Center, Emeryville, California 94608, and 5 Departments of Psychiatry and Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California 94143
µ-Opioid receptor (MOR) desensitization and endocytosis have been implicated in tolerance and dependence to opioids. The efficiency of each process is known to be agonist dependent; however, it is not known what determines the relative efficiency of various agonists at either process. In the present study, homologous MOR desensitization in locus ceruleus (LC) neurons and MOR internalization in HEK293 cells were examined using a series of agonists. The results show that the rank order of this series of agonists was different when comparing the magnitude of hyperpolarization and the ability to cause desensitization in LC neurons. Endocytosis of MOR was also examined in HEK293 cells using the same agonists. The relative ability to cause endocytosis in HEK293 cells correlated with the degree of desensitization in LC cells. This strong correlation suggests that the two processes are closely linked. The results also suggest that agonist efficacy is not necessarily a predictor of the ability to cause MOR desensitization or endocytosis. Identification and characterization of the biophysical properties of agonists that favor desensitization and internalization of receptors will lead to a better understanding of opioid signaling.
Key words: opioids; locus ceruleus; homologous desensitization; endocytosis; electrophysiology; imaging
* V.A.A. and S.A. contributed equally to this work.
Copyright © 2002 Society for Neuroscience 0270-6474/02/22135769-08$05.00/0
This article has been cited by other articles:
A. Ravindranathan, G. Joslyn, M. Robertson, M. A. Schuckit, J. L. Whistler, and R. L. White
Functional characterization of human variants of the mu-opioid receptor gene
PNAS, June 30, 2009; 106(26): 10811 - 10816.
[Abstract] [Full Text] [PDF]
R. Lu, Y. Li, Y. Zhang, Y. Chen, A. D. Shields, D. G. Winder, T. Angelotti, K. Jiao, L. E. Limbird, Y. Zhou, et al.
Epitope-tagged Receptor Knock-in Mice Reveal That Differential Desensitization of {alpha}2-Adrenergic Responses Is because of Ligand-selective Internalization
J. Biol. Chem., May 8, 2009; 284(19): 13233 - 13243.
[Abstract] [Full Text] [PDF]
Y. J. Yu, S. Arttamangkul, C. J. Evans, J. T. Williams, and M. von Zastrow
Neurokinin 1 Receptors Regulate Morphine-Induced Endocytosis and Desensitization of {micro}-Opioid Receptors in CNS Neurons
J. Neurosci., January 7, 2009; 29(1): 222 - 233.
[Abstract] [Full Text] [PDF]
L. Zhang, L. F. Brass, and D. R. Manning
The Gq and G12 Families of Heterotrimeric G Proteins Report Functional Selectivity
Mol. Pharmacol., January 1, 2009; 75(1): 235 - 241.
[Abstract] [Full Text] [PDF]
S. Arttamangkul, N. Quillinan, M. J. Low, M. von Zastrow, J. Pintar, and J. T. Williams
Differential Activation and Trafficking of {micro}-Opioid Receptors in Brain Slices
Mol. Pharmacol., October 1, 2008; 74(4): 972 - 979.
[Abstract] [Full Text] [PDF]
A. Gupta, R. Rozenfeld, I. Gomes, K. M. Raehal, F. M. Decaillot, L. M. Bohn, and L. A. Devi
Post-activation-mediated Changes in Opioid Receptors Detected by N-terminal Antibodies
J. Biol. Chem., April 18, 2008; 283(16): 10735 - 10744.
[Abstract] [Full Text] [PDF]
M. S. Virk and J. T. Williams
Agonist-Specific Regulation of {micro}-Opioid Receptor Desensitization and Recovery from Desensitization
Mol. Pharmacol., April 1, 2008; 73(4): 1301 - 1308.
[Abstract] [Full Text] [PDF]
D. Thompson, M. Pusch, and J. L. Whistler
Changes in G Protein-coupled Receptor Sorting Protein Affinity Regulate Postendocytic Targeting of G Protein-coupled Receptors
J. Biol. Chem., October 5, 2007; 282(40): 29178 - 29185.
[Abstract] [Full Text] [PDF]
W. Walwyn, C. J. Evans, and T. G. Hales
{beta}-Arrestin2 and c-Src Regulate the Constitutive Activity and Recycling of {micro} Opioid Receptors in Dorsal Root Ganglion Neurons
J. Neurosci., May 9, 2007; 27(19): 5092 - 5104.
[Abstract] [Full Text] [PDF]
D. Liao, O. O. Grigoriants, H. H. Loh, and P.-Y. Law
Agonist-Dependent Postsynaptic Effects of Opioids on Miniature Excitatory Postsynaptic Currents in Cultured Hippocampal Neurons
J Neurophysiol, February 1, 2007; 97(2): 1485 - 1494.
[Abstract] [Full Text] [PDF]
J. D. Urban, W. P. Clarke, M. von Zastrow, D. E. Nichols, B. Kobilka, H. Weinstein, J. A. Javitch, B. L. Roth, A. Christopoulos, P. M. Sexton, et al.
Functional Selectivity and Classical Concepts of Quantitative Pharmacology
J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 1 - 13.
[Abstract] [Full Text] [PDF]
S. Arttamangkul, M. Torrecilla, K. Kobayashi, H. Okano, and J. T. Williams
Separation of {micro}-Opioid Receptor Desensitization and Internalization: Endogenous Receptors in Primary Neuronal Cultures
J. Neurosci., April 12, 2006; 26(15): 4118 - 4125.
[Abstract] [Full Text] [PDF]
V. C. Dang and J. T. Williams
Morphine-Induced {micro}-Opioid Receptor Desensitization
Mol. Pharmacol., October 1, 2005; 68(4): 1127 - 1132.
[Abstract] [Full Text] [PDF]
Z. Zuo
The Role of Opioid Receptor Internalization and {beta}-Arrestins in the Development of Opioid Tolerance
Anesth. Analg., September 1, 2005; 101(3): 728 - 734.
[Abstract] [Full Text] [PDF]
H. Haberstock-Debic, K.-A. Kim, Y. J. Yu, and M. von Zastrow
Morphine Promotes Rapid, Arrestin-Dependent Endocytosis of {micro}-Opioid Receptors in Striatal Neurons
J. Neurosci., August 24, 2005; 25(34): 7847 - 7857.
[Abstract] [Full Text] [PDF]
S. E. Bartlett, J. Enquist, F. W. Hopf, J. H. Lee, F. Gladher, V. Kharazia, M. Waldhoer, W. S. Mailliard, R. Armstrong, A. Bonci, et al.
Dopamine responsiveness is regulated by targeted sorting of D2 receptors
PNAS, August 9, 2005; 102(32): 11521 - 11526.
[Abstract] [Full Text] [PDF]
C. A. McClung, E. J. Nestler, and V. Zachariou
Regulation of Gene Expression by Chronic Morphine and Morphine Withdrawal in the Locus Ceruleus and Ventral Tegmental Area
J. Neurosci., June 22, 2005; 25(25): 6005 - 6015.
[Abstract] [Full Text] [PDF]
M. A. Simmons
Functional Selectivity, Ligand-Directed Trafficking, Conformation-Specific Agonism: What's In A Name?
Mol. Interv., June 1, 2005; 5(3): 154 - 157.
[Abstract] [Full Text] [PDF]
N. Shimoyama, M. Shimoyama, A. M. Davis, D. T. Monaghan, and C. E. Inturrisi
An Antisense Oligonucleotide to the N-Methyl-D-aspartate (NMDA) Subunit NMDAR1 Attenuates NMDA-Induced Nociception, Hyperalgesia, and Morphine Tolerance
J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 834 - 840.
[Abstract] [Full Text] [PDF]
B. M. Cox
Agonists at {micro}-Opioid Receptors Spin the Wheels to Keep the Action Going
Mol. Pharmacol., January 1, 2005; 67(1): 12 - 14.
[Abstract] [Full Text] [PDF]
T. Koch, A. Widera, K. Bartzsch, S. Schulz, L.-O. Brandenburg, N. Wundrack, A. Beyer, G. Grecksch, and V. Hollt
Receptor Endocytosis Counteracts the Development of Opioid Tolerance
Mol. Pharmacol., January 1, 2005; 67(1): 280 - 287.
[Abstract] [Full Text] [PDF]
C. P. Bailey, E. Kelly, and G. Henderson
Protein Kinase C Activation Enhances Morphine-Induced Rapid Desensitization of {micro}-Opioid Receptors in Mature Rat Locus Ceruleus Neurons
Mol. Pharmacol., December 1, 2004; 66(6): 1592 - 1598.
[Abstract] [Full Text] [PDF]
V. C. Dang and J. T. Williams
Chronic Morphine Treatment Reduces Recovery from Opioid Desensitization
J. Neurosci., September 1, 2004; 24(35): 7699 - 7706.
[Abstract] [Full Text] [PDF]
I. Tegeder and G. Geisslinger
Opioids As Modulators of Cell Death and Survival--Unraveling Mechanisms and Revealing New Indications
Pharmacol. Rev., September 1, 2004; 56(3): 351 - 369.
[Abstract] [Full Text] [PDF]
B. M. Cox and A. T. Crowder
Receptor Domains Regulating {micro} Opioid Receptor Uncoupling and Internalization: Relevance to Opioid Tolerance
Mol. Pharmacol., March 1, 2004; 65(3): 492 - 495.
[Full Text] [PDF]
J. Celver, M. Xu, W. Jin, J. Lowe, and C. Chavkin
Distinct Domains of the {micro}-Opioid Receptor Control Uncoupling and Internalization
Mol. Pharmacol., March 1, 2004; 65(3): 528 - 537.
[Abstract] [Full Text] [PDF]
C. P. Bailey, D. Couch, E. Johnson, K. Griffiths, E. Kelly, and G. Henderson
{micro}-Opioid Receptor Desensitization in Mature Rat Neurons: Lack of Interaction between DAMGO and Morphine
J. Neurosci., November 19, 2003; 23(33): 10515 - 10520.
[Abstract] [Full Text] [PDF]
M. Tan, M. Groszer, A. M. Tan, A. Pandya, X. Liu, and C.-W. Xie
Phosphoinositide 3-Kinase Cascade Facilitates {micro}-Opioid Desensitization in Sensory Neurons by Altering G-Protein-Effector Interactions
J. Neurosci., November 12, 2003; 23(32): 10292 - 10301.
[Abstract] [Full Text] [PDF]
B. Song and J. C. G. Marvizon
Dorsal Horn Neurons Firing at High Frequency, But Not Primary Afferents, Release Opioid Peptides that Produce {micro}-Opioid Receptor Internalization in the Rat Spinal Cord
J. Neurosci., October 8, 2003; 23(27): 9171 - 9184.
[Abstract] [Full Text] [PDF]
S. L. Borgland, M. Connor, P. B. Osborne, J. B. Furness, and M. J. Christie
Opioid Agonists Have Different Efficacy Profiles for G Protein Activation, Rapid Desensitization, and Endocytosis of Mu-opioid Receptors
J. Biol. Chem., May 23, 2003; 278(21): 18776 - 18784.
[Abstract] [Full Text] [PDF]
J.-G. Li, F. Zhang, X.-L. Jin, and L.-Y. Liu-Chen
Differential Regulation of the Human kappa Opioid Receptor by Agonists: Etorphine and Levorphanol Reduced Dynorphin A- and U50,488H-Induced Internalization and Phosphorylation
J. Pharmacol. Exp. Ther., May 1, 2003; 305(2): 531 - 540.
[Abstract] [Full Text] [PDF]
M. B. Patel, C. N. Patel, V. Rajashekara, and B. C. Yoburn
Opioid Agonists Differentially Regulate {micro}-Opioid Receptors and Trafficking Proteins in Vivo
Mol. Pharmacol., December 1, 2002; 62(6): 1464 - 1470.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|