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The effect of propofol on actin, ERK-1/2 and GABA(A) receptor content in neurones

Oscarsson, A.; Juhas, Maria LU ; Sjölander, Anita LU and Eintrei, C. (2007) In Acta Anaesthesiologica Scandinavica 51(9). p.1184-1189
Abstract
Aim: Interaction with the gamma-aminobutyric acid receptor (GABA(A)R) complex is recognized as an important component of the mechanism of many anaesthetic agents, including propofol. The aims of this study were to investigate the effect of propofol on GABA(A)R, to determine whether exposure of neurones to propofol influences the localization of GABA(A)R within the cell and to look for cytoskeletal changes that may be connected with activation, such as the mitogen-activated protein kinase (MAPK) pathway. Methods: Primary cortical cell cultures from rat, with and without pre-incubation with the GABA(A)R antagonist bicuculline, were exposed to propofol. The cells were lysed and separated into membrane and cytosolic fractions. Immunoblot... (More)
Aim: Interaction with the gamma-aminobutyric acid receptor (GABA(A)R) complex is recognized as an important component of the mechanism of many anaesthetic agents, including propofol. The aims of this study were to investigate the effect of propofol on GABA(A)R, to determine whether exposure of neurones to propofol influences the localization of GABA(A)R within the cell and to look for cytoskeletal changes that may be connected with activation, such as the mitogen-activated protein kinase (MAPK) pathway. Methods: Primary cortical cell cultures from rat, with and without pre-incubation with the GABA(A)R antagonist bicuculline, were exposed to propofol. The cells were lysed and separated into membrane and cytosolic fractions. Immunoblot analyses of filamentous actin (F-actin), the GABA(A) beta(2)-subunit receptor and extracellular signal-regulated kinase-1/2 (ERK-1/2) were performed. Results: Propofol triggers an increase in GABA(A)R, actin content and ERK-1/2 phosphorylation in the cytosolic fraction. In the membrane fraction, there is a decrease in GABA(A) beta(2)-subunit content and an increase in both actin content and ERK-1/2 phosphorylation. The GABA(A)R antagonist bicuculline blocks the propofol-induced changes in F-actin, ERK and GABA(A) beta(2)-subunit content, and ERK-1/2 phosphorylation. Conclusion: We believe that propofol triggers a dose-dependent internalization of the GABA(A) beta(2)-subunit. The increase in internal GABA(A) beta(2)-subunit content exhibits a close relationship to actin polymerization and to an increase in ERK-1/2 activation. Actin contributes to the internalization sequestering of the GABA(A) beta(2)-subunit. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
propofol, mitogen-activated protein kinase (MAPK), actin, extracellular signal-regulated kinase-1/2 (ERK-1/2), gamma-aminobutyric, acid receptor.
in
Acta Anaesthesiologica Scandinavica
volume
51
issue
9
pages
1184 - 1189
publisher
Wiley-Blackwell
external identifiers
  • wos:000249376200010
  • scopus:34548551205
ISSN
0001-5172
DOI
10.1111/j.1399-6576.2007.01388.x
language
English
LU publication?
yes
id
cc374d79-50f0-4660-b418-9aa4c401231a (old id 686948)
date added to LUP
2007-12-19 11:00:56
date last changed
2017-01-01 04:24:30
@article{cc374d79-50f0-4660-b418-9aa4c401231a,
  abstract     = {Aim: Interaction with the gamma-aminobutyric acid receptor (GABA(A)R) complex is recognized as an important component of the mechanism of many anaesthetic agents, including propofol. The aims of this study were to investigate the effect of propofol on GABA(A)R, to determine whether exposure of neurones to propofol influences the localization of GABA(A)R within the cell and to look for cytoskeletal changes that may be connected with activation, such as the mitogen-activated protein kinase (MAPK) pathway. Methods: Primary cortical cell cultures from rat, with and without pre-incubation with the GABA(A)R antagonist bicuculline, were exposed to propofol. The cells were lysed and separated into membrane and cytosolic fractions. Immunoblot analyses of filamentous actin (F-actin), the GABA(A) beta(2)-subunit receptor and extracellular signal-regulated kinase-1/2 (ERK-1/2) were performed. Results: Propofol triggers an increase in GABA(A)R, actin content and ERK-1/2 phosphorylation in the cytosolic fraction. In the membrane fraction, there is a decrease in GABA(A) beta(2)-subunit content and an increase in both actin content and ERK-1/2 phosphorylation. The GABA(A)R antagonist bicuculline blocks the propofol-induced changes in F-actin, ERK and GABA(A) beta(2)-subunit content, and ERK-1/2 phosphorylation. Conclusion: We believe that propofol triggers a dose-dependent internalization of the GABA(A) beta(2)-subunit. The increase in internal GABA(A) beta(2)-subunit content exhibits a close relationship to actin polymerization and to an increase in ERK-1/2 activation. Actin contributes to the internalization sequestering of the GABA(A) beta(2)-subunit.},
  author       = {Oscarsson, A. and Juhas, Maria and Sjölander, Anita and Eintrei, C.},
  issn         = {0001-5172},
  keyword      = {propofol,mitogen-activated protein kinase (MAPK),actin,extracellular signal-regulated kinase-1/2 (ERK-1/2),gamma-aminobutyric,acid receptor.},
  language     = {eng},
  number       = {9},
  pages        = {1184--1189},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Anaesthesiologica Scandinavica},
  title        = {The effect of propofol on actin, ERK-1/2 and GABA(A) receptor content in neurones},
  url          = {http://dx.doi.org/10.1111/j.1399-6576.2007.01388.x},
  volume       = {51},
  year         = {2007},
}