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The effect of 4β-phorbol-12,13-dibutyrate and staurosporine on the extracellular glutamate levels during ischemia in the rat striatum

Boris-Möller, Fredrik and Wieloch, Tadeusz LU (1998) In Molecular and Chemical Neuropathology 35(1-3). p.133-147
Abstract

Hypothermia diminishes the ischemia-induced protein kinase C (PKC) translocation and inhibition, and also reduces transmitter release during ischemia. To study the role of PKC in the mechanism of glutamate release during ischemia, we measured extracellular glutamate levels in the striatum with the microdialysis technique, in the presence and absence in the dialysate of the PKC activator 4β-phorbol-12,13-dibutyrate (PDBu) and the protein kinase inhibitor staurosporine. We confirm that hypothermia attenuates the elevation of extracellular levels of glutamate in the striatum during ischemia. In the presence of PDBu, the glutamate levels in the dialysate increased from 0.3 μmol/L to an end ischemic level of 4.8 μmol/L during hypothermic... (More)

Hypothermia diminishes the ischemia-induced protein kinase C (PKC) translocation and inhibition, and also reduces transmitter release during ischemia. To study the role of PKC in the mechanism of glutamate release during ischemia, we measured extracellular glutamate levels in the striatum with the microdialysis technique, in the presence and absence in the dialysate of the PKC activator 4β-phorbol-12,13-dibutyrate (PDBu) and the protein kinase inhibitor staurosporine. We confirm that hypothermia attenuates the elevation of extracellular levels of glutamate in the striatum during ischemia. In the presence of PDBu, the glutamate levels in the dialysate increased from 0.3 μmol/L to an end ischemic level of 4.8 μmol/L during hypothermic ischemia (33°C). These levels were significantly higher than in hypothermic ischemia (33°C) without added PDBu. Staurosporine significantly mitigated the glutamate levels during normothermic ischemia. Our data suggest that PKC is involved in the temperature-dependent elevations of extracellular glutamate levels in the striatum during ischemia, and we propose that compounds preventing PKC activation may mimic the hypothermic protective action against ischemic brain damage. ©Copyright 1999 by Humana Press Inc. All rights of any nature, whatsoever, reserved.

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author
organization
publishing date
type
Contribution to journal
publication status
published
keywords
Brain, Glutamate, Hypothermia, Ischemia, Microdialysis, Protein kinase C
in
Molecular and Chemical Neuropathology
volume
35
issue
1-3
pages
133 - 147
external identifiers
  • Scopus:0032915522
ISSN
1044-7393
DOI
10.1007/BF02815120
language
English
LU publication?
yes
id
53acd06f-f5c7-4ee1-b3fb-aeb03f6475de
date added to LUP
2016-10-05 16:04:14
date last changed
2016-11-29 10:14:33
@misc{53acd06f-f5c7-4ee1-b3fb-aeb03f6475de,
  abstract     = {<p>Hypothermia diminishes the ischemia-induced protein kinase C (PKC) translocation and inhibition, and also reduces transmitter release during ischemia. To study the role of PKC in the mechanism of glutamate release during ischemia, we measured extracellular glutamate levels in the striatum with the microdialysis technique, in the presence and absence in the dialysate of the PKC activator 4β-phorbol-12,13-dibutyrate (PDBu) and the protein kinase inhibitor staurosporine. We confirm that hypothermia attenuates the elevation of extracellular levels of glutamate in the striatum during ischemia. In the presence of PDBu, the glutamate levels in the dialysate increased from 0.3 μmol/L to an end ischemic level of 4.8 μmol/L during hypothermic ischemia (33°C). These levels were significantly higher than in hypothermic ischemia (33°C) without added PDBu. Staurosporine significantly mitigated the glutamate levels during normothermic ischemia. Our data suggest that PKC is involved in the temperature-dependent elevations of extracellular glutamate levels in the striatum during ischemia, and we propose that compounds preventing PKC activation may mimic the hypothermic protective action against ischemic brain damage. ©Copyright 1999 by Humana Press Inc. All rights of any nature, whatsoever, reserved.</p>},
  author       = {Boris-Möller, Fredrik and Wieloch, Tadeusz},
  issn         = {1044-7393},
  keyword      = {Brain,Glutamate,Hypothermia,Ischemia,Microdialysis,Protein kinase C},
  language     = {eng},
  number       = {1-3},
  pages        = {133--147},
  series       = {Molecular and Chemical Neuropathology},
  title        = {The effect of 4β-phorbol-12,13-dibutyrate and staurosporine on the extracellular glutamate levels during ischemia in the rat striatum},
  url          = {http://dx.doi.org/10.1007/BF02815120},
  volume       = {35},
  year         = {1998},
}