Biased μ-opioid receptor agonists diversely regulate lateral mobility and functional coupling of the receptor to its cognate G proteins

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F16%3A10333261" target="_blank" >RIV/00216208:11310/16:10333261 - isvavai.cz</a>

Result on the web

<a href="http://link.springer.com/article/10.1007%2Fs00210-016-1293-8" target="_blank" >http://link.springer.com/article/10.1007%2Fs00210-016-1293-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00210-016-1293-8" target="_blank" >10.1007/s00210-016-1293-8</a>

Result language

angličtina

Original language name

Biased μ-opioid receptor agonists diversely regulate lateral mobility and functional coupling of the receptor to its cognate G proteins

Original language description

There are some indications that biased μ-opioid ligands may diversely affect μ-opioid receptor (MOR) properties. Here, we used confocal fluorescence recovery after photobleaching (FRAP) to study the regulation by different MORagonistsofreceptormovementwithintheplasmamembrane of HEK293 cells stably expressing a functional yellow fluorescent protein (YFP)-tagged μ-opioid receptor (MORYFP). We found that the lateral mobility of MOR-YFP was increased by (D-Ala2,N-MePhe4,Gly5-ol)-enkephalin (DAMGO) and to a lesser extent also by morphine but decreased by endomorphin-2. Interestingly, cholesterol depletion strongly enhanced the ability of morphine to elevate receptor mobility but significantly reduced or even eliminated the effect of DAMGO and endomorphin-2, respectively. Moreover, the ability of DAMGO and endomorphin-2 to influence MOR-YFP movement was diminished by pertussis toxin treatment. The results obtained by agonist-stimulated [35S]GTPγSbindingassaysindicatedthatDAMGOexhibited higher efficacy than morphine and endomorphin-2 did and that the efficacy of DAMGO, contrary to the latter agonists, was enhanced by cholesterol depletion. Overall, our study provides clear evidence that biased MOR agonists diversely affect receptor mobility in plasma membranes as well as MOR/G protein coupling and that the regulatory effect of different ligands depends on the membrane cholesterol content. These findings help to delineate the fundamental properties of MOR regarding their interaction with biased MOR ligands and cognate G proteins.

Czech name

—

Czech description

—

Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

ED - Physiology

OECD FORD branch

—

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Naunyn-Schmiedeberg's Archives of Pharmacology

ISSN

0028-1298

e-ISSN

—

Volume of the periodical

2016

Issue of the periodical within the volume

389

Country of publishing house

DE - GERMANY

Number of pages

12

Pages from-to

1289-1300

UT code for WoS article

000387847400004

EID of the result in the Scopus database

2-s2.0-84986296962