Signaling Events Initiated by Kappa Opioid Receptor Activation: Quantification and Immunocolocalization Using Phospho-Selective KOR, p38 MAPK, and KIR 3.1 Antibodies
Open accessAbstract
Psychiatric disorders including anxiety, depression, and addiction are both precipitated and exacerbated by severe or chronic stress exposure. While acutely, stress responses are adaptive, repeated exposure to stress can dysregulate the brain in such a way as to predispose the organism to both physiological and mental illness. Understanding the neuronal chemicals, cell types, and circuits involved in both normal and pathological stress responses are essential in developing new therapeutics for psychiatric diseases. Varying degrees of stressor exposure cause the release of a constellation of chemicals, including neuropeptides such as dynorphin. Neuropeptidergic release can be very difficult to directly measure with adequate spatial and temporal resolution. Moreover, the downstream consequences following release and receptor binding are numerous and also difficult to measure with cellular resolution. Following repeated stressor exposure, dynorphin is released, binds to the kappa opioid receptor (KOR), and causes activation of KOR. Agonist-activated KOR becomes a substrate for G protein receptor kinase (GRK), which phosphorylates the Ser369 residue at the C-terminal tail of the receptor in the first step in the β-Arrestin-dependent desensitization cascade. Through the use of phospho--selective antibodies developed and validated in the laboratory, we have the tools, to assess with fine cellular resolution, the strength of behavioral stimulus required for release, time course of the release, and regional location of release. We have gone on to show that following KOR activation, both ERK 1/2 and p38 MAP kinase phosphorylation are increased through use of commercially available phospho-selective antibodies. Finally, we have identified that one effector of KOR/p38MAP kinase is K(IR) 3.1 and have developed a phospho-selective antibody against the Y12 motif of this channel. Much like KOR and p38 MAP kinase, phosphorylation of this potassium channel increases following repeated stress. The following chapter discusses immunohistochemical and quantification methods used for phospho-selective antibodies used in various brain regions following behavioral manipulations.
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MAPK1 activation is altered after stress and corticosterone exposure, and MAPK signaling was proposed to regulate antidepressant modulation of glial cell line-derived neurotrophic factor.
“It is known that MAPK1 activation is altered after stress [31] and corticosterone exposure [32] and that MAPK signaling was proposed to regulate AD modulation of glial cell line-derived neurotrophic factor [33].”
From The Impact of BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 Genetic Polymorphisms in Antidepressant Treatment Response Phenotypes (2023) · cites this paper as [31]
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“It is known that MAPK1 activation is altered after stress [31] and corti-”
Background
- Authors
- Lemos, J. C., Roth, C. A., & Chavkin, C.
- Affiliations
- University of Washington (US)
- Corresponding author
- Lemos, Julia C.
- Venue
- Methods in Molecular Biology
- Publisher
- Humana Press
- Published
- 2011
- Volume
- 717
- Pages
- 197-219
- ISSN
- 1064-3745 (ISSN-L)
- 1940-6029
- PMC
- PMC3727639
- OpenAlex
- W3390919
- Cited by
- 16
- References
- 13
- Citations by year
- 2023: 1 · 2022: 2 · 2021: 3 · 2019: 2 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 1.79
- Type
- book chapter
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- Locations
- Methods in molecular biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R01DA030074, K05DA020570, R01DA016898, R37DA011672)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- kappa opioid receptor, dynorphin, chronic stress, p38 MAPK, ERK1/2, receptor phosphorylation, G protein-coupled receptor kinases, depression, addiction
- MeSH terms
- Animals, Brain, Cell Line, Chromatography, Affinity, Humans, Immunohistochemistry, Microscopy, Signal Transduction, Receptors, Opioid, kappa, Mitogen-Activated Protein Kinase 1, Potassium Channels, Inwardly Rectifying, Antibodies, Phospho-Specific, p38 Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Mice, Rats
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