AJP - Heart Watch the video to learn how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol (July 31, 2003). doi:10.1152/ajpheart.00520.2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
285/6/H2592    most recent
00520.2003v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (33)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sharp, C. D.
Right arrow Articles by Alexander, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sharp, C. D.
Right arrow Articles by Alexander, J. S.
Submitted on June 4, 2003
Accepted on July 28, 2003

Glutamate Causes a Loss in Human Cerebral Endothelial Barrier Integrity through the Activation of the N-Methyl-D-Aspartate Receptor (NMDAR)

Christopher D. Sharp1*, I, Hines1, J. Houghton1, A. Warren1, T. H. Jackson, IV1, A. Jawahar2, A. Nanda2, J. W. Elrod1, A. Long1, A. Minagar3, and J. S. Alexander1

1 Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, LA, USA
2 Department of Neurosurgery, LSU Health Sciences Center, Shreveport, LA, USA
3 Department of Neurology, LSU Health Sciences Center, Shreveport, LA, USA

* To whom correspondence should be addressed. E-mail: csharp{at}lsuhsc.edu.

L-glutamate, is a major excitatory neurotransmitter which binds ionotropic and metabotropic glutamate receptors. Cerebral endothelial cells from many species have been shown to express several forms of glutamate receptors; however, to date, human cerebral endothelial cells have not been shown to express either NMDA receptor message or protein. This study provides evidence that human cerebral endothelial cells express message and protein for NMDA receptors. Human cerebral endothelial cell monolayer electrical resistance changes in response to glutamate receptor agonists, antagonists and second message blockers were tested. RT-PCR and Western analysis were used to demonstrate the presence of the NMDA receptor. Glutamate and NMDA (1mM) caused a significant decrease in electrical resistance compared to sham control at 2 hours post exposure; this response could be blocked significantly by MK-801 (an NMDA antagonist), TMB-8 (an intracellular Ca2+ antagonist) and NAC (an antioxidant). tACPD (a metabotropic receptor agonist) at 1mM did not significantly decrease electrical resistance. Our results are consistent with a model where glutamate, at excitotoxic levels, may lead to a breakdown in the blood brain barrier via activation of NMDA receptors.




This article has been cited by other articles:


Home page
 StrokeHome page
C. R.W. Kuhlmann, L. Librizzi, D. Closhen, T. Pflanzner, V. Lessmann, C. U. Pietrzik, M. de Curtis, and H. J. Luhmann
Mechanisms of C-Reactive Protein-Induced Blood-Brain Barrier Disruption * Supplemental Methods
Stroke, April 1, 2009; 40(4): 1458 - 1466.
[Abstract] [Full Text] [PDF]

Home page
 Annals of Clinical & Laboratory ScienceHome page
K. S. McCully
Chemical Pathology of Homocysteine. IV. Excitotoxicity, Oxidative Stress, Endothelial Dysfunction, and Inflammation
Ann. Clin. Lab. Sci., January 1, 2009; 39(3): 219 - 232.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
F. Domoki, B. Kis, T. Gaspar, F. Bari, and D. W. Busija
Cerebromicrovascular endothelial cells are resistant to L-glutamate
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1099 - R1108.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
O. Handa, J. Stephen, and G. Cepinskas
Role of endothelial nitric oxide synthase-derived nitric oxide in activation and dysfunction of cerebrovascular endothelial cells during early onsets of sepsis
Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1712 - H1719.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
B. Bauer, A. M. S. Hartz, A. Pekcec, K. Toellner, D. S. Miller, and H. Potschka
Seizure-Induced Up-Regulation of P-Glycoprotein at the Blood-Brain Barrier through Glutamate and Cyclooxygenase-2 Signaling
Mol. Pharmacol., May 1, 2008; 73(5): 1444 - 1453.
[Abstract] [Full Text] [PDF]

Home page
 Mult SclerHome page
R.E. Gonsette
Review: Oxidative stress and excitotoxicity: a therapeutic issue in multiple sclerosis?
Multiple Sclerosis, January 1, 2008; 14(1): 22 - 34.
[Abstract] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
H. Parfenova, S. Basuroy, S. Bhattacharya, D. Tcheranova, Y. Qu, R. F. Regan, and C. W. Leffler
Glutamate induces oxidative stress and apoptosis in cerebral vascular endothelial cells: contributions of HO-1 and HO-2 to cytoprotection
Am J Physiol Cell Physiol, May 1, 2006; 290(5): C1399 - C1410.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
C. W. Leffler, H. Parfenova, J. H. Jaggar, and R. Wang
Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation
J Appl Physiol, March 1, 2006; 100(3): 1065 - 1076.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
C. D. Sharp, J. Houghton, J. W. Elrod, A. Warren, T. H. Jackson IV, A. Jawahar, A. Nanda, A. Minagar, and J. S. Alexander
N-methyl-D-aspartate receptor activation in human cerebral endothelium promotes intracellular oxidant stress
Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1893 - H1899.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1976 by the American Physiological Society.