Evidence map›Paper›PMID 9870938›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience1999

Requirement of receptor internalization for opioid stimulation of mitogen-activated protein kinase: biochemical and immunofluorescence confocal microscopic evidence.

E G Ignatova, M M Belcheva, L M Bohn, M C Neuman, C J Coscia

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
7.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 128 citations in OpenAlex.

  1. Article
  2. Article
  3. Endosomal signaling of delta opioid receptors is an endogenous mechanism and therapeutic target for relief from inflammatory pain.Proceedings of the National Academy of Sciences of the United States of America · 2020
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  18. Article
  19. Post-transcriptional regulation of opioid receptors in the nervous system.Frontiers in bioscience : a journal and virtual library · 2004
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

E G IgnatovaE. A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA.
M M Belcheva
L M Bohn
M C Neuman
C J Coscia
Saint Louis University · US

Funding

OPIOID MODULATION OF ASTROCYTE PROLIFERATIONR01DA005412 · NIDA · SAINT LOUIS UNIVERSITY · PI COSCIA, CARMINE JAMES · 1987 to 2008
$2.3M
OPIOID EFFECTS IN C6 GLIOMA CELLSF31DA005766 · NIDA · SAINT LOUIS UNIVERSITY · PI BOHN, LAURA M · 1996 to 1998
–
NIDA NIH HHS DA05412NIDA NIH HHS F31 DA005766NIDA NIH HHS R01 DA005412
6 · The paper itself

Abstract

Previously, we implicated the opioid receptor (OR), Gbetagamma subunits, and Ras in the opioid activation of extracellular signal-regulated protein kinase (ERK), a member of the mitogen-activated protein (MAP) kinase family involved in mitogenic signaling. We now report that OR endocytosis also plays a role in the opioid stimulation of ERK activity. COS-7 and HEK-293 cells were cotransfected with the cDNA of delta-, mu;-, or kappa-OR, dynamin wild-type (DWT), or the dominant suppressor mutant dynamin K44A, which blocks receptor endocytosis. The activation of ERK by opioid agonists in the presence of DWT was detected. In contrast, parallel ectopic coexpression of the K44A mutant with OR, followed by agonist treatment, resulted in a time-dependent attenuation of ERK activation. Immunofluorescence confocal microscopy of delta-OR and DWT-cotransfected COS-7 cells revealed that agonist exposure for 10 min resulted in an ablation of cell surface delta-OR immunoreactivity (IR) and an intensification of cytoplasmic (presumably endosomal) staining as seen in the absence of overexpressed DWT. After 1 hr of delta-agonist exposure the cells displayed substantial internalization of delta-OR IR. If the cells were cotransfected with delta-OR and dynamin mutant K44A, OR IR was retained on the cell surface even after 1 hr of delta-agonist treatment. Parallel immunofluorescence confocal microscopy, using an anti-ERK antibody, showed that agonist-induced time-dependent ERK IR trafficking into perinuclear and nuclear loci was impaired in the internalization-defective cells. Thus, both biochemical and immunofluorescence confocal microscopic evidence supports the hypothesis that the opioid activation of ERK requires receptor internalization in transfected mammalian cells.

Indexed as

AnimalsBiological TransportCalcium-Calmodulin-Dependent Protein KinasesCOS CellsDynaminsEnkephalin, D-Penicillamine (2,5)-Enkephalin, Leucine-2-AlanineEnkephalinsGTP PhosphohydrolasesImmunohistochemistryMicroscopy, ConfocalNaltrexoneNarcotic AntagonistsReceptors, OpioidSignal TransductionStimulation, ChemicalCalcium-Calmodulin-Dependent Protein KinasesDynaminsEnkephalin, D-Penicillamine (2,5)-Enkephalin, Leucine-2-AlanineEnkephalinsGTP PhosphohydrolasesNaltrexoneNarcotic AntagonistsReceptors, Opioid

Identifiers

PMID9870938
PMCPMC2504521
OpenAlexW1918531995

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.