Ionotropic glutamate receptors in cerebral microvascular endothelium are functionally linked to heme oxygenase

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Vasodilator effects of glutamate in the cerebral circulation are, in part, mediated by carbon monoxide (CO), which is formed from heme via the heme oxygenase (HO) pathway. The hypothesis addressed was that glutamate receptors (GluRs) in cerebral microvascular endothelium are functionally linked to HO. Using a radioligand binding and immunoblotting, GluRs were characterized in cerebral microvascular endothelial cells (CMVEC) from newborn pigs. High-affinity (80 nmol/L) reversible binding of [3H]glutamate ([3H]Glu) was detected in CMVEC membranes. The N-methyl-D-aspartate (NMDA) receptor ligands - NMDA, quinolinic acid, (±)1-aminocyclopentane-cis-1,3-dicarboxylic acid (cis-ACPD), AP5, 4C3HPG, and CPP - and the (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor ligands - AMPA, kainic acid, quisqualic acid, DNQX, and CNQX - displaced 20% to 30% of bound [3H]Glu in CMVEC membranes. Metabotropic GluRs antagonists (4CPG, PHCC, and CPPG) did not displace bound [3H]Glu. L-Aspartate, an agonist of GluRs and glutamate transporters, displaced 80% or more of bound [3H]Glu. Ionotropic (NR1 and GluR1) and metabotropic (mGluR1α) GluRs were detected in CMVEC by immunoblotting. Glutamate, aspartate, cis-ACPD, AMPA, (RS)-2-amino-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA), and kainate (10-5 mol/L) increased HO-directed CO formation by isolated cerebral microvessels and by cultured CMVEC. These data in newborn pigs suggest that CMVEC express ionotropic GluRs that are functionally linked to HO. GluR-mediated increases in CO formation by vascular endothelium may result in increase in cerebral blood flow.

Original languageEnglish (US)
Pages (from-to)190-197
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume23
Issue number2
DOIs
StatePublished - Feb 1 2003

Fingerprint

Ionotropic Glutamate Receptors
Heme Oxygenase (Decyclizing)
Endothelium
Endothelial Cells
Cerebrovascular Circulation
Glutamate Receptors
Carbon Monoxide
Glutamic Acid
Metabotropic Glutamate Receptors
Kainic Acid
Immunoblotting
Aspartic Acid
Swine
Cell Membrane
Quisqualic Acid
Quinolinic Acid
Ligands
6-Cyano-7-nitroquinoxaline-2,3-dione
Isoxazoles
Kainic Acid Receptors

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

@article{c4f5c4a666fe4706bf07149786836f16,
title = "Ionotropic glutamate receptors in cerebral microvascular endothelium are functionally linked to heme oxygenase",
abstract = "Vasodilator effects of glutamate in the cerebral circulation are, in part, mediated by carbon monoxide (CO), which is formed from heme via the heme oxygenase (HO) pathway. The hypothesis addressed was that glutamate receptors (GluRs) in cerebral microvascular endothelium are functionally linked to HO. Using a radioligand binding and immunoblotting, GluRs were characterized in cerebral microvascular endothelial cells (CMVEC) from newborn pigs. High-affinity (80 nmol/L) reversible binding of [3H]glutamate ([3H]Glu) was detected in CMVEC membranes. The N-methyl-D-aspartate (NMDA) receptor ligands - NMDA, quinolinic acid, (±)1-aminocyclopentane-cis-1,3-dicarboxylic acid (cis-ACPD), AP5, 4C3HPG, and CPP - and the (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor ligands - AMPA, kainic acid, quisqualic acid, DNQX, and CNQX - displaced 20{\%} to 30{\%} of bound [3H]Glu in CMVEC membranes. Metabotropic GluRs antagonists (4CPG, PHCC, and CPPG) did not displace bound [3H]Glu. L-Aspartate, an agonist of GluRs and glutamate transporters, displaced 80{\%} or more of bound [3H]Glu. Ionotropic (NR1 and GluR1) and metabotropic (mGluR1α) GluRs were detected in CMVEC by immunoblotting. Glutamate, aspartate, cis-ACPD, AMPA, (RS)-2-amino-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA), and kainate (10-5 mol/L) increased HO-directed CO formation by isolated cerebral microvessels and by cultured CMVEC. These data in newborn pigs suggest that CMVEC express ionotropic GluRs that are functionally linked to HO. GluR-mediated increases in CO formation by vascular endothelium may result in increase in cerebral blood flow.",
author = "Elena Parfenova and Alex Fedinec and Charles Leffler",
year = "2003",
month = "2",
day = "1",
doi = "10.1097/01.WCB.000004823561824.C4",
language = "English (US)",
volume = "23",
pages = "190--197",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Ionotropic glutamate receptors in cerebral microvascular endothelium are functionally linked to heme oxygenase

AU - Parfenova, Elena

AU - Fedinec, Alex

AU - Leffler, Charles

PY - 2003/2/1

Y1 - 2003/2/1

N2 - Vasodilator effects of glutamate in the cerebral circulation are, in part, mediated by carbon monoxide (CO), which is formed from heme via the heme oxygenase (HO) pathway. The hypothesis addressed was that glutamate receptors (GluRs) in cerebral microvascular endothelium are functionally linked to HO. Using a radioligand binding and immunoblotting, GluRs were characterized in cerebral microvascular endothelial cells (CMVEC) from newborn pigs. High-affinity (80 nmol/L) reversible binding of [3H]glutamate ([3H]Glu) was detected in CMVEC membranes. The N-methyl-D-aspartate (NMDA) receptor ligands - NMDA, quinolinic acid, (±)1-aminocyclopentane-cis-1,3-dicarboxylic acid (cis-ACPD), AP5, 4C3HPG, and CPP - and the (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor ligands - AMPA, kainic acid, quisqualic acid, DNQX, and CNQX - displaced 20% to 30% of bound [3H]Glu in CMVEC membranes. Metabotropic GluRs antagonists (4CPG, PHCC, and CPPG) did not displace bound [3H]Glu. L-Aspartate, an agonist of GluRs and glutamate transporters, displaced 80% or more of bound [3H]Glu. Ionotropic (NR1 and GluR1) and metabotropic (mGluR1α) GluRs were detected in CMVEC by immunoblotting. Glutamate, aspartate, cis-ACPD, AMPA, (RS)-2-amino-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA), and kainate (10-5 mol/L) increased HO-directed CO formation by isolated cerebral microvessels and by cultured CMVEC. These data in newborn pigs suggest that CMVEC express ionotropic GluRs that are functionally linked to HO. GluR-mediated increases in CO formation by vascular endothelium may result in increase in cerebral blood flow.

AB - Vasodilator effects of glutamate in the cerebral circulation are, in part, mediated by carbon monoxide (CO), which is formed from heme via the heme oxygenase (HO) pathway. The hypothesis addressed was that glutamate receptors (GluRs) in cerebral microvascular endothelium are functionally linked to HO. Using a radioligand binding and immunoblotting, GluRs were characterized in cerebral microvascular endothelial cells (CMVEC) from newborn pigs. High-affinity (80 nmol/L) reversible binding of [3H]glutamate ([3H]Glu) was detected in CMVEC membranes. The N-methyl-D-aspartate (NMDA) receptor ligands - NMDA, quinolinic acid, (±)1-aminocyclopentane-cis-1,3-dicarboxylic acid (cis-ACPD), AP5, 4C3HPG, and CPP - and the (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor ligands - AMPA, kainic acid, quisqualic acid, DNQX, and CNQX - displaced 20% to 30% of bound [3H]Glu in CMVEC membranes. Metabotropic GluRs antagonists (4CPG, PHCC, and CPPG) did not displace bound [3H]Glu. L-Aspartate, an agonist of GluRs and glutamate transporters, displaced 80% or more of bound [3H]Glu. Ionotropic (NR1 and GluR1) and metabotropic (mGluR1α) GluRs were detected in CMVEC by immunoblotting. Glutamate, aspartate, cis-ACPD, AMPA, (RS)-2-amino-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA), and kainate (10-5 mol/L) increased HO-directed CO formation by isolated cerebral microvessels and by cultured CMVEC. These data in newborn pigs suggest that CMVEC express ionotropic GluRs that are functionally linked to HO. GluR-mediated increases in CO formation by vascular endothelium may result in increase in cerebral blood flow.

UR - http://www.scopus.com/inward/record.url?scp=0037313972&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037313972&partnerID=8YFLogxK

U2 - 10.1097/01.WCB.000004823561824.C4

DO - 10.1097/01.WCB.000004823561824.C4

M3 - Article

VL - 23

SP - 190

EP - 197

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 2

ER -