Chronic opioid antagonist administration upregulates mu opioid receptor binding without altering mu opioid receptor mRNA levels

1995 ◽  
Vol 33 (2) ◽  
pp. 351-355 ◽  
Author(s):  
Ellen M. Unterwald ◽  
Joshua M. Rubenfeld ◽  
Yasuo Imai ◽  
Jia-Bei Wang ◽  
George R. Uhl ◽  
...  
1990 ◽  
Vol 5 (5) ◽  
pp. 497-506 ◽  
Author(s):  
R.A. Giolli ◽  
R.H.I. Blanks ◽  
Y. Torigoe ◽  
R.J. Clarke ◽  
J.H. Fallon ◽  
...  

AbstractThe presence and concentrations of each of the three subtypes of opioid receptors (mu, kappa, and delta) has been studied in the accessory optic nuclei (dorsal, lateral, and medial terminal nuclei and the interstitial nucleus of the superior fasciculus, posterior fibers: DTN, LTN, MTN, and inSFp) in normal young rats with radioligands directed towards each opioid receptor subtype. The changes in mu opioid receptors have also been investigated in monocularly enucleated rats in which one eye was removed and the rats sacrificed at postoperative day (PO) 2, 3, 5, 7, 14, and 30. As the MTN is the only accessory optic nucleus of the rat large enough for semiquantitative evaluation, the mu receptor population of the MTN has been subjected to optical microdensitometric analysis.All four of the accessory optic nuclei (AOS nuclei) are found to contain exceedingly high levels of mu opioid receptor binding with the selective radioligand [3H]-[D-Ala, MePhe4, Gly-ol5] (DAGO), low levels of kappa opioid receptor binding using the radioligand [3H]-[ethylketocyclazocine] (EKC) together with the competing agents [D-Pro4]-morphiceptin and [D-Ser2, Thr6]-Leu-enkephalin, and an absence of delta opioid receptor binding with the radioligand [3H]-[D-A1a2, D-Leu5]-enkephalin (DADLE) combined with the competing agent [D-Pro4]-morphiceptin. Monocular enucleation, as studied on the mu opioid receptor population with this experimental approach, results in virtually a complete loss of mu opioid receptors throughout all four of the contralaterally located AOS nuclei, including both dorsal and ventral subdivisions of the medial terminal nucleus (MTNd, v). Kappa and delta receptors are very few (kappa receptors) or are lacking (delta receptors) in the AOS nuclei, and for this reason, the effects of monocular enucleation on these two opioid receptor subtypes have not been investigated. Monocular enucleation also produces a significant lowering in mu receptor binding in other primary optic nuclei (the lateral geniculate nuclei, nucleus of the optic tract, and superficial layers of the superior colliculus) and in the pars principalis of the medial geniculate nucleus (description of changes in mu receptors in non-accessory optic primary optic nuclei will be considered elsewhere).Microdensitometric study of the MTNd, v shows that the decreased binding of mu receptors in this nucleus is barely detectable (about 6%) at PO2 and rises to 6–15% at PO3. At PO5 receptor loss reaches approximately 62%, whereas at PO7 it is about 81% complete. At PO14 and PO30, the mu receptor loss is nearly complete at around 93%. Mu receptor loss involves all of the AOS nuclei contralateral, but none ipsilateral, to ocular enucleation, an observation entirely consistent with the overwhelmingly crossed (about 97%) nature of the retinofugal projection to the rat accessory optic nuclei. These opioid receptors represent a prominent feature in the AOS and other primary optic nuclei of the rat. Their role in visuomotor control remains uncertain but probably involves the fine-tuning of information concerned with compensatory eye movements.


2010 ◽  
Vol 11 (4) ◽  
pp. S30
Author(s):  
C. Campbell ◽  
H. Kuwabara ◽  
M. Simango ◽  
J. Campbell ◽  
J. Haythornthwaite ◽  
...  

2002 ◽  
Vol 58 (3) ◽  
pp. 285-288 ◽  
Author(s):  
Eugene D Festa ◽  
Christine Cecala ◽  
Vanya Quinones-Jenab ◽  
Shirzad Jenab

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e113694 ◽  
Author(s):  
Hiroto Kuwabara ◽  
Stephen J. Heishman ◽  
James R. Brasic ◽  
Carlo Contoreggi ◽  
Nicola Cascella ◽  
...  

1999 ◽  
Vol 48 (1) ◽  
pp. 109-112 ◽  
Author(s):  
Vadim Yuferov ◽  
Yan Zhou ◽  
Rudolph Spangler ◽  
Christopher E Maggos ◽  
Ann Ho ◽  
...  

Neuropeptides ◽  
1984 ◽  
Vol 5 (1-3) ◽  
pp. 117-120 ◽  
Author(s):  
James W. Lewis ◽  
Michael E. Lewis ◽  
Deborah J. Loomus ◽  
Huda Akil

2011 ◽  
Vol 12 (4) ◽  
pp. P80
Author(s):  
S. Bounds ◽  
C. Campbell ◽  
H. Kuwabara ◽  
J. Campbell ◽  
R. Edwards ◽  
...  

2003 ◽  
Vol 44 (1) ◽  
pp. 111-116 ◽  
Author(s):  
R. Ortiz-Butron ◽  
J. Pacheco-Rosado ◽  
A. Hernández-Garcia ◽  
M. Briones-Velasco ◽  
L. Rocha

1997 ◽  
Vol 87 (5) ◽  
pp. 1127-1138 ◽  
Author(s):  
Elizabeth K. Gies ◽  
Dawn M. Peters ◽  
Carol R. Gelb ◽  
Kathleen M. Knag ◽  
Robert A. Peterfreund

Background The mu opioid receptor (MuOR) is a member of the superfamily of G protein-coupled receptors that mediates the analgesic actions of endogenous opioid peptides and the narcotic alkaloid derivatives of morphine. Activation and translocation of protein kinase C (PKC) by N-methyl-D-aspartate receptor stimulation correlates with resistance to opioid drugs in experimental states of neuropathic pain, but the cellular mechanisms of resistance have not been identified. One possibility is that PKC activation regulates MuOR mRNA expression and thus the ability to generate functional receptors. Using a human neuroblastoma cell line, the authors tested the hypothesis that phorbol ester activation of PKC regulates MuOR mRNA levels. Methods SH-SY5Y cells were maintained in a continuous monolayer culture and treated with phorbol esters or other agents before extraction of total cellular RNA. Slot-blot hybridization was used to measure the level of MuOR mRNA using 32P-labeled MuOR cDNA probes under high-stringency conditions. Autoradiograms were analyzed by scanning and densitometry. Results MuOR mRNA levels decreased in a dose- and time-dependent manner after tetradecanoyl phorbol acetate (TPA) was administered to activate PKC. The nadir, a level of approximately 50% of control, was at 2-8 h, followed by gradual recovery. The actions of TPA were blocked by pretreatment with the selective PKC inhibitor bisindolylmaleimide, but not by inhibition of protein synthesis with cycloheximide or anisomycin. The combination of TPA treatment and transcription inhibition with actinomycin D was associated with a transient increase in MuOR mRNA. Conclusions Mu opioid receptor mRNA levels are regulated by activation of PKC in a neuronal model. Protein kinase C effects which decrease MuOR mRNA levels appear largely independent of new protein synthesis, and cytotoxicity does not account for the findings. Plasticity of MuOR gene expression may contribute to variations in clinical responses to opioid analgesics in clinical states such as neuropathic pain.


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