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Arrestin-Mediated Activation of p38 MAPK: Molecular Mechanisms and Behavioral Consequences

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Arrestins - Pharmacology and Therapeutic Potential

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 219))

Abstract

Studies of kappa opioid receptor signaling mechanisms during the last decade have demonstrated that agonist activation of the receptor results in Gβγ-dependent signaling and distinct arrestin-dependent signaling events. Gβγ-dependent signaling results in ion channel regulation causing neuronal inhibition, inhibition of transmitter release, and subsequent analgesic responses. In contrast, arrestin-dependent signaling events result in p38 MAPK activation and subsequent dysphoric and proaddictive behavioral responses. Resolution of these two branches of signaling cascades has enabled strategies designed to identify pathway-selective drugs that may have unique therapeutic utilities.

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Abbreviations

ASK1:

Apoptosis signal-regulating kinase 1

β2AR:

β2-Adrenergic receptor

CRF:

Corticotropin-releasing factor

JNK:

c-Jun N-terminal Kinase

ERK1/2:

Extracellular signal-regulated kinase

GRK:

G-protein receptor kinase

GPCRs:

G-protein-coupled receptors

GIRK, Kir3:

G-protein-gated inwardly rectifying potassium channel

GFAP:

Glial fibrillary acidic protein

KOR:

Kappa opioid receptor

rKOR:

Rodent KOR

hKOR:

Human KOR

MAPK:

Mitogen-activated protein kinase

MAP3K5:

Mitogen-activated protein kinase kinase kinase 5

PKC:

Protein kinase C

5HT:

Serotonin, 5-hydroxytryptamine

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Acknowledgments

We are grateful to our coauthors on the research papers from our lab cited in this review for their creativity and hard work. The studies cited were largely supported by research grants from the National Institute on Drug Abuse, currently R37DA11672, RO1DA030074, T32DA07278, and KO5DA020570.

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Authors and Affiliations

  1. Department of Pharmacology, University of Washington, Seattle, WA, 98195, USA

    Charles Chavkin, Selena S. Schattauer & Jamie R. Levin

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  1. Charles Chavkin
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  2. Selena S. Schattauer
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  3. Jamie R. Levin
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Corresponding author

Correspondence to Charles Chavkin .

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Editors and Affiliations

  1. Professor of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

    Vsevolod V. Gurevich

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Chavkin, C., Schattauer, S.S., Levin, J.R. (2014). Arrestin-Mediated Activation of p38 MAPK: Molecular Mechanisms and Behavioral Consequences. In: Gurevich, V. (eds) Arrestins - Pharmacology and Therapeutic Potential. Handbook of Experimental Pharmacology, vol 219. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-41199-1_14

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