Ionotropic glutamate receptors in cerebral microvascular endothelium are functionally linked to heme oxygenase
| Autor: | Charles W. Leffler, Alex Fedinec, Helena Parfenova |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Kainic acid
Swine Glutamic Acid Kainate receptor AMPA receptor Biology Ligands Binding Competitive 030218 nuclear medicine & medical imaging 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Excitatory Amino Acid Agonists Animals Quisqualic acid Cells Cultured Cerebral Cortex Aspartic Acid Carbon Monoxide Binding Sites Microcirculation Glutamate receptor Molecular biology Metabotropic receptor Neurology chemistry Biochemistry Receptors Glutamate Cerebrovascular Circulation Heme Oxygenase (Decyclizing) NMDA receptor Neurology (clinical) Endothelium Vascular Cardiology and Cardiovascular Medicine 030217 neurology & neurosurgery Ionotropic effect |
| Zdroj: | Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 23(2) |
| ISSN: | 0271-678X |
| Popis: | 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 [H]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. |
| Databáze: | OpenAIRE |
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