Prolonged Morphine Treatment Alters Expression and Plasma Membrane Distribution of beta-Adrenergic Receptors and Some Other Components of Their Signaling System in Rat Cerebral Cortex

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F17%3A10368555" target="_blank" >RIV/00216208:11310/17:10368555 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s12031-017-0987-9" target="_blank" >http://dx.doi.org/10.1007/s12031-017-0987-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s12031-017-0987-9" target="_blank" >10.1007/s12031-017-0987-9</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Prolonged Morphine Treatment Alters Expression and Plasma Membrane Distribution of beta-Adrenergic Receptors and Some Other Components of Their Signaling System in Rat Cerebral Cortex

Popis výsledku v původním jazyce

beta-Adrenergic signaling plays an important role in regulating diverse brain functions and alterations in this signaling have been observed in different neuropathological conditions. In this study, we investigated the effect of a 10-day treatment with high doses of morphine (10 mg/kg per day) on major components and functional state of the beta-adrenergic receptor (beta-AR) signaling system in the rat cerebral cortex. beta-ARs were characterized by radioligand binding assays and amounts of various G protein subunits, adenylyl cyclase (AC) isoforms, G protein-coupled receptor kinases (GRKs), and beta-arrestin were examined by Western blot analysis. AC activity was determined as a measure of functionality of the signaling system. We also assessed the partitioning of selected signaling proteins between the lipid raft and non-raft fractions prepared from cerebrocortical plasma membranes. Morphine treatment resulted in a significant upregulation of beta-ARs, GRK3, and some AC isoforms (AC-I, -II, and -III). There was no change in quantity of G proteins and some other signaling molecules (AC-IV, AC-V/VI, GRK2, GRK5, GRK6, and beta-arrestin) compared with controls. Interestingly, morphine exposure caused a partial redistribution of beta-ARs, G(s)alpha, G(o)alpha, and GRK2 between lipid rafts and bulk plasma membranes. Spatial localization of other signaling molecules within the plasma membrane was not changed. Basal as well as fluoride- and forskolin-stimulated AC activities were not significantly different in membrane preparations from control and morphine-treated animals. However, AC activity stimulated by the beta-AR agonist isoprenaline was markedly increased. This is the first study to demonstrate lipid raft association of key components of the cortical beta-AR system and its sensitivity to morphine.

Název v anglickém jazyce

Prolonged Morphine Treatment Alters Expression and Plasma Membrane Distribution of beta-Adrenergic Receptors and Some Other Components of Their Signaling System in Rat Cerebral Cortex

Popis výsledku anglicky

beta-Adrenergic signaling plays an important role in regulating diverse brain functions and alterations in this signaling have been observed in different neuropathological conditions. In this study, we investigated the effect of a 10-day treatment with high doses of morphine (10 mg/kg per day) on major components and functional state of the beta-adrenergic receptor (beta-AR) signaling system in the rat cerebral cortex. beta-ARs were characterized by radioligand binding assays and amounts of various G protein subunits, adenylyl cyclase (AC) isoforms, G protein-coupled receptor kinases (GRKs), and beta-arrestin were examined by Western blot analysis. AC activity was determined as a measure of functionality of the signaling system. We also assessed the partitioning of selected signaling proteins between the lipid raft and non-raft fractions prepared from cerebrocortical plasma membranes. Morphine treatment resulted in a significant upregulation of beta-ARs, GRK3, and some AC isoforms (AC-I, -II, and -III). There was no change in quantity of G proteins and some other signaling molecules (AC-IV, AC-V/VI, GRK2, GRK5, GRK6, and beta-arrestin) compared with controls. Interestingly, morphine exposure caused a partial redistribution of beta-ARs, G(s)alpha, G(o)alpha, and GRK2 between lipid rafts and bulk plasma membranes. Spatial localization of other signaling molecules within the plasma membrane was not changed. Basal as well as fluoride- and forskolin-stimulated AC activities were not significantly different in membrane preparations from control and morphine-treated animals. However, AC activity stimulated by the beta-AR agonist isoprenaline was markedly increased. This is the first study to demonstrate lipid raft association of key components of the cortical beta-AR system and its sensitivity to morphine.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Journal of Molecular Neuroscience

ISSN

0895-8696

e-ISSN

—

Svazek periodika

63

Číslo periodika v rámci svazku

3-4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

364-376

Kód UT WoS článku

000415983800011

EID výsledku v databázi Scopus

2-s2.0-85032393137