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A tyrosine kinase regulates propofol-induced modulation of the beta-subunit of the GABA(A) receptor and release of intracellular calcium in cortical rat neurones

Bjornstrom, K; Sjölander, Anita LU ; Schippert, A and Eintrei, C (2002) In Acta Physiologica Scandinavica1888-12-31+01:002006-01-01+01:00 175(3). p.227-235
Abstract
Propofol, an intravenous anaesthetic, has been shown to interact with the beta -subunit of the gamma -amino butyric acid(A) (GABA(A) ) receptor and also to cause changes in [Ca2+ ](i) . The GABA(A) receptor, a suggested target for anaesthetics, is known to be regulated by kinases. We have investigated if tyrosine kinase is involved in the intracellular signal system used by propofol to cause anaesthesia. We used primary cell cultured neurones from newborn rats, pre-incubated with or without a tyrosine kinase inhibitor before propofol stimulation. The effect of propofol on tyrosine phosphorylation and changes in [Ca2+ ](i) were investigated. Propofol (3 mu g mL(-1) , 16.8 mu M) increased intracellular calcium levels by 122 +/- 34% (mean +/-... (More)
Propofol, an intravenous anaesthetic, has been shown to interact with the beta -subunit of the gamma -amino butyric acid(A) (GABA(A) ) receptor and also to cause changes in [Ca2+ ](i) . The GABA(A) receptor, a suggested target for anaesthetics, is known to be regulated by kinases. We have investigated if tyrosine kinase is involved in the intracellular signal system used by propofol to cause anaesthesia. We used primary cell cultured neurones from newborn rats, pre-incubated with or without a tyrosine kinase inhibitor before propofol stimulation. The effect of propofol on tyrosine phosphorylation and changes in [Ca2+ ](i) were investigated. Propofol (3 mu g mL(-1) , 16.8 mu M) increased intracellular calcium levels by 122 +/- 34% (mean +/- SEM) when applied to neurones in calcium free medium. This rise in [Ca2+ ](i) was lowered by 68% when the cells were pre-incubated with the tyrosine kinase inhibitor herbimycin A before exposure to propofol (P < 0.05). Propofol caused an increase (33 +/- 10%) in tyrosine phosphorylation, with maximum at 120 s, of the beta -subunit of the GABA(A) -receptor. This tyrosine phosphorylation was decreased after pre-treatment with herbimycin A (44 +/- 7%, P < 0.05), and was not affected by the absence of exogenous calcium in the medium. Tyrosine kinase participates in the propofol signalling system by inducing the release of calcium from intracellular stores and by modulating the beta -subunit of the GABA(A) -receptor. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
6-di-isopropylphenol, 2, anaesthetic mechanisms, intravenous, tyrosine kinase, rat, propofol, neurone
in
Acta Physiologica Scandinavica1888-12-31+01:002006-01-01+01:00
volume
175
issue
3
pages
227 - 235
publisher
Wiley-Blackwell
external identifiers
  • pmid:12100362
  • wos:000176514100007
  • scopus:0035991552
ISSN
0001-6772
DOI
10.1046/j.1365-201X.2002.00991.x
language
English
LU publication?
yes
id
44f4c9ed-ddb8-4d28-adf0-7f376815197b (old id 334244)
date added to LUP
2007-08-02 13:50:20
date last changed
2017-11-27 13:21:32
@article{44f4c9ed-ddb8-4d28-adf0-7f376815197b,
  abstract     = {Propofol, an intravenous anaesthetic, has been shown to interact with the beta -subunit of the gamma -amino butyric acid(A) (GABA(A) ) receptor and also to cause changes in [Ca2+ ](i) . The GABA(A) receptor, a suggested target for anaesthetics, is known to be regulated by kinases. We have investigated if tyrosine kinase is involved in the intracellular signal system used by propofol to cause anaesthesia. We used primary cell cultured neurones from newborn rats, pre-incubated with or without a tyrosine kinase inhibitor before propofol stimulation. The effect of propofol on tyrosine phosphorylation and changes in [Ca2+ ](i) were investigated. Propofol (3 mu g mL(-1) , 16.8 mu M) increased intracellular calcium levels by 122 +/- 34% (mean +/- SEM) when applied to neurones in calcium free medium. This rise in [Ca2+ ](i) was lowered by 68% when the cells were pre-incubated with the tyrosine kinase inhibitor herbimycin A before exposure to propofol (P &lt; 0.05). Propofol caused an increase (33 +/- 10%) in tyrosine phosphorylation, with maximum at 120 s, of the beta -subunit of the GABA(A) -receptor. This tyrosine phosphorylation was decreased after pre-treatment with herbimycin A (44 +/- 7%, P &lt; 0.05), and was not affected by the absence of exogenous calcium in the medium. Tyrosine kinase participates in the propofol signalling system by inducing the release of calcium from intracellular stores and by modulating the beta -subunit of the GABA(A) -receptor.},
  author       = {Bjornstrom, K and Sjölander, Anita and Schippert, A and Eintrei, C},
  issn         = {0001-6772},
  keyword      = {6-di-isopropylphenol,2,anaesthetic mechanisms,intravenous,tyrosine kinase,rat,propofol,neurone},
  language     = {eng},
  number       = {3},
  pages        = {227--235},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Physiologica Scandinavica1888-12-31+01:002006-01-01+01:00},
  title        = {A tyrosine kinase regulates propofol-induced modulation of the beta-subunit of the GABA(A) receptor and release of intracellular calcium in cortical rat neurones},
  url          = {http://dx.doi.org/10.1046/j.1365-201X.2002.00991.x},
  volume       = {175},
  year         = {2002},
}