Regulators of G protein signaling attenuate opioid inhibition of adenylyl cyclase in a permeabilized C6 cell model

Jeffery N Talbot; David L Roman; Richard R Neubig; John R Traynor

doi:10.1096/fasebj.20.4.A255-c

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Regulators of G protein signaling attenuate opioid inhibition of adenylyl cyclase in a permeabilized C6 cell model

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Regulators of G protein signaling attenuate opioid inhibition of adenylyl cyclase in a permeabilized C6 cell model

Jeffery N Talbot, David L Roman, Richard R Neubig and John R Traynor

The FASEB journal, Vol.20(4), pp.A255-A255

03/2006

DOI: 10.1096/fasebj.20.4.A255-c

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Abstract

Regulators of G protein signaling (RGS) proteins terminate G protein signaling by accelerating the rate of GTP hydrolysis of Gα subunits. Recent evidence implicates RGS proteins as key players in shaping the response to both acute and chronic opioids, but the relative contribution of individual RGS proteins in these processes is poorly understood. In order to determine the effects of specific, purified RGS proteins on opioid signaling C6 cells stably expressing the mu opioid receptor were rendered permeable to ions and proteins by treatment with digitonin. Forskolin stimulation of adenylyl cyclase (AC) was equipotent in permeabilized vs. non‐permeabilized cells. DAMGO, a mu‐specific opioid peptide, inhibited forskolin‐sitmulated AC activity with slightly reduced potency in permeabilized cells (18±1.7 nM) compared to non‐permeabilized cells (4.0±1.3 nM) but was equally efficacious under either condition, indicating that opioid signaling to AC remained fully intact under permeabilization conditions. Purified RGS4 box domain added to permeabilized cells resulted in as much as a two‐fold loss in DAMGO potency but had no effect in cells expressing RGS‐insensitive G proteins. Also, the inhibitory effect of DAMGO was reduced to the same extent and in a non‐additive manner by full length RGS4 and RGS8. In contrast, RGS7 box had no effect. These data suggest that specific RGS proteins differentially regulate opioid signaling to adenylyl cyclase and that a permeabilized cell model is useful for studying the effects of specific RGS proteins on aspects of G protein‐coupled receptor signaling. Supported by DA04087, GM39561, T32 DA007268

Details

Title: Subtitle: Regulators of G protein signaling attenuate opioid inhibition of adenylyl cyclase in a permeabilized C6 cell model
Creators: Jeffery N Talbot - University of Michigan Medical School
David L Roman - University of Michigan Medical School
Richard R Neubig - University of Michigan Medical School
John R Traynor - University of Michigan Medical School
Resource Type: Journal article
Publication Details: The FASEB journal, Vol.20(4), pp.A255-A255
Publisher: Federation of American Societies for Experimental Biology
DOI: 10.1096/fasebj.20.4.A255-c
ISSN: 0892-6638
eISSN: 1530-6860
Number of pages: 1
Language: English
Date published: 03/2006
Academic Unit: Pharmacy; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
Record Identifier: 9984071989402771

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