Functional selectivity of 6′-guanidinonaltrindole (6′-GNTI) at κ-opioid receptors in striatal neurons

Cullen L. Schmid; John M. Streicher; Chad E. Groer; Thomas A. Munro; Lei Zhou; Laura M. Bohn

doi:10.1074/jbc.M113.476234

Functional selectivity of 6′-guanidinonaltrindole (6′-GNTI) at κ-opioid receptors in striatal neurons

Cullen L. Schmid, John M. Streicher, Chad E. Groer, Thomas A. Munro, Lei Zhou, Laura M. Bohn

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

Abstract

Background: 6′-Guanidinonaltrindole (6′-GNTI) activates G protein coupling to κ-opioid receptors (KOR) without β-arrestin2 recruitment in transfected cells. Results: In striatal neurons, 6′-GNTI activates Akt but not ERK1/2; U69,593 activates both kinases. Conclusion: In neurons, U69,593-induced activation of ERK1/2 is β-arrestin2-dependent, whereas activation of Akt is G protein-mediated. Significance: Identification of KOR signaling pathways in endogenous systems will inform the development of KOR-directed medications.

Original language	English (US)
Pages (from-to)	22387-22398
Number of pages	12
Journal	Journal of Biological Chemistry
Volume	288
Issue number	31
DOIs	https://doi.org/10.1074/jbc.M113.476234
State	Published - Aug 2 2013
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

Access to Document

10.1074/jbc.M113.476234

Cite this

@article{4a5453e0e85248739989d88a01f9a637,

title = "Functional selectivity of 6′-guanidinonaltrindole (6′-GNTI) at κ-opioid receptors in striatal neurons",

abstract = "Background: 6′-Guanidinonaltrindole (6′-GNTI) activates G protein coupling to κ-opioid receptors (KOR) without β-arrestin2 recruitment in transfected cells. Results: In striatal neurons, 6′-GNTI activates Akt but not ERK1/2; U69,593 activates both kinases. Conclusion: In neurons, U69,593-induced activation of ERK1/2 is β-arrestin2-dependent, whereas activation of Akt is G protein-mediated. Significance: Identification of KOR signaling pathways in endogenous systems will inform the development of KOR-directed medications.",

author = "Schmid, {Cullen L.} and Streicher, {John M.} and Groer, {Chad E.} and Munro, {Thomas A.} and Lei Zhou and Bohn, {Laura M.}",

year = "2013",

month = aug,

day = "2",

doi = "10.1074/jbc.M113.476234",

language = "English (US)",

volume = "288",

pages = "22387--22398",

journal = "Journal of Biological Chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology Inc.",

number = "31",

}

TY - JOUR

T1 - Functional selectivity of 6′-guanidinonaltrindole (6′-GNTI) at κ-opioid receptors in striatal neurons

AU - Schmid, Cullen L.

AU - Streicher, John M.

AU - Groer, Chad E.

AU - Munro, Thomas A.

AU - Zhou, Lei

AU - Bohn, Laura M.

PY - 2013/8/2

Y1 - 2013/8/2

N2 - Background: 6′-Guanidinonaltrindole (6′-GNTI) activates G protein coupling to κ-opioid receptors (KOR) without β-arrestin2 recruitment in transfected cells. Results: In striatal neurons, 6′-GNTI activates Akt but not ERK1/2; U69,593 activates both kinases. Conclusion: In neurons, U69,593-induced activation of ERK1/2 is β-arrestin2-dependent, whereas activation of Akt is G protein-mediated. Significance: Identification of KOR signaling pathways in endogenous systems will inform the development of KOR-directed medications.

AB - Background: 6′-Guanidinonaltrindole (6′-GNTI) activates G protein coupling to κ-opioid receptors (KOR) without β-arrestin2 recruitment in transfected cells. Results: In striatal neurons, 6′-GNTI activates Akt but not ERK1/2; U69,593 activates both kinases. Conclusion: In neurons, U69,593-induced activation of ERK1/2 is β-arrestin2-dependent, whereas activation of Akt is G protein-mediated. Significance: Identification of KOR signaling pathways in endogenous systems will inform the development of KOR-directed medications.

UR - http://www.scopus.com/inward/record.url?scp=84881236758&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881236758&partnerID=8YFLogxK

U2 - 10.1074/jbc.M113.476234

DO - 10.1074/jbc.M113.476234

M3 - Article

C2 - 23775075

AN - SCOPUS:84881236758

SN - 0021-9258

VL - 288

SP - 22387

EP - 22398

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 31

ER -

Functional selectivity of 6′-guanidinonaltrindole (6′-GNTI) at κ-opioid receptors in striatal neurons

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this