 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 11, 2574-2581, Copyright © 1991 by Society for Neuroscience
Transient homologous mu-opioid receptor desensitization in rat locus coeruleus neurons
GC Harris and JT Williams
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Opioid agonists hyperpolarize neurons of the locus coeruleus (LC) in the
slice preparation. When opioids were applied at concentrations that caused
a maximum hyperpolarization, the membrane potential hyperpolarized to a
peak (about 30 mV) in the first minute and then declined over a period of 5
min. In addition, following the washout, the amplitude of the
hyperpolarization induced by a lower concentration of opioid was
significantly reduced as compared to control. The original response to both
the low and the high concentrations of opioid recovered after removal of
opioids for about 20 min. The decline in response, termed "acute
desensitization," was observed only with concentrations of opioids that
caused a maximum hyperpolarization and was dependent on the concentration
of opioid applied (EC50 for [Met5]- enkephalin (ME), between 3 and 5
microM). The response to ME (300 nM) was reduced to 6% of control following
washout of a 5-min application of ME (30 microM), whereas the response to
noradrenaline (300 nM) was reduced to 75% of control. The acute
desensitization therefore was selective for the opioid receptor with
marginal cross-desensitization to the alpha 2-adrenoceptor-mediated
hyperpolarization. The desensitization still occurred following treatment
with beta- chlornaltrexamine (beta-CNA), to decrease receptor reserve, as
well as in cells taken from animals treated chronically with morphine. The
mechanism for the acute desensitization was investigated using agents
thought to alter kinase activity. This acute desensitization may represent
an initial stage in the development of tolerance produced by chronic
administration of opioids.
This article has been cited by other articles:
|
|
|
|
 
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
J. L. Leaney, A. Benians, S. Brown, M. Nobles, D. Kelly, and A. Tinker
Rapid desensitization of G protein-gated inwardly rectifying K+ currents is determined by G protein cycle
Am J Physiol Cell Physiol,
July 1, 2004;
287(1):
C182 - C191.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Sickmann and C. Alzheimer
Short-Term Desensitization of G-Protein-Activated, Inwardly Rectifying K+ (GIRK) Currents in Pyramidal Neurons of Rat Neocortex
J Neurophysiol,
October 1, 2003;
90(4):
2494 - 2503.
[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]
|
|
|
|
|
|
|
V. A. Alvarez, S. Arttamangkul, V. Dang, A. Salem, J. L. Whistler, M. von Zastrow, D. K. Grandy, and J. T. Williams
{micro}-Opioid Receptors: Ligand-Dependent Activation of Potassium Conductance, Desensitization, and Internalization
J. Neurosci.,
July 1, 2002;
22(13):
5769 - 5776.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Blanchet and C. Luscher
Desensitization of {micro}-opioid receptor-evoked potassium currents: Initiation at the receptor, expression at the effector
PNAS,
March 21, 2002;
(2002)
72075399.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ivanov and G. Aston-Jones
Local Opiate Withdrawal in Locus Coeruleus Neurons In Vitro
J Neurophysiol,
June 1, 2001;
85(6):
2388 - 2397.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. T. Williams, M. J. Christie, and O. Manzoni
Cellular and Synaptic Adaptations Mediating Opioid Dependence
Physiol Rev,
January 1, 2001;
81(1):
299 - 343.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Beaumont, M. B. Hepworth, J. S. Luty, E. Kelly, and G. Henderson
Somatostatin Receptor Desensitization in NG108-15 Cells. A CONSEQUENCE OF RECEPTOR SEQUESTRATION
J. Biol. Chem.,
December 11, 1998;
273(50):
33174 - 33183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z Shui, I A Khan, H Tsuga, T Haga, and M R Boyett
Role of receptor kinase in short-term desensitization of cardiac muscarinic K+ channels expressed in Chinese hamster ovary cells
J. Physiol.,
March 1, 1998;
507(2):
325 - 334.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Noble and B. M. Cox
The Role of Dopaminergic Systems in Opioid Receptor Desensitization in Nucleus Accumbens and Caudate Putamen of Rat After Chronic Morphine Treatment
J. Pharmacol. Exp. Ther.,
November 1, 1997;
283(2):
557 - 565.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. Kovoor, V. Nappey, B. L. Kieffer, and C. Chavkin
µ and delta Opioid Receptors Are Differentially Desensitized by the Coexpression of beta -Adrenergic Receptor Kinase 2 and beta -Arrestin 2 in Xenopus Oocytes
J. Biol. Chem.,
October 31, 1997;
272(44):
27605 - 27611.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Wagner, G. Zhang, A. H. Lagrange, O. K. Rønnekleiv, and M. J. Kelly
Tolerance to µ-Opioid Receptor Agonists but not Cross-tolerance to gamma -Aminobutyric AcidB Receptor Agonists in Arcuate A12 Dopamine Neurons with Chronic Morphine Treatment
J. Pharmacol. Exp. Ther.,
February 1, 1997;
280(2):
1057 - 1064.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
E. J. Van Bockstaele, E. E. O. Colago, P. Cheng, A. Moriwaki, G. R. Uhl, and V. M. Pickel
Ultrastructural Evidence for Prominent Distribution of the µ-Opioid Receptor at Extrasynaptic Sites on Noradrenergic Dendrites in the Rat Nucleus Locus Coeruleus
J. Neurosci.,
August 15, 1996;
16(16):
5037 - 5048.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kovoor, D. J. Henry, and C. Chavkin
Agonist-induced Desensitization of the Mu Opioid Receptor-coupled Potassium Channel (GIRK1)
J. Biol. Chem.,
January 13, 1995;
270(2):
589 - 595.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Blanchet and C. Luscher
Desensitization of {micro}-opioid receptor-evoked potassium currents: Initiation at the receptor, expression at the effector
PNAS,
April 2, 2002;
99(7):
4674 - 4679.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
