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.
Keywords
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- 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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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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