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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

ED - Fyziologie

OECD FORD obor

—

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Naunyn-Schmiedeberg's Archives of Pharmacology

ISSN

0028-1298

e-ISSN

—

Svazek periodika

2016

Číslo periodika v rámci svazku

389

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

12

Strana od-do

1289-1300

Kód UT WoS článku

000387847400004

EID výsledku v databázi Scopus

2-s2.0-84986296962