Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular $ Ca^{2+} $ signals and nitric oxide release in human brain microvascular endothelial cells
Abstract Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity causes an increase in local cerebral blood flow (CBF) to ensure local supply of oxygen and nutrients to the activated areas. The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-d-aspart...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Negri, Sharon [verfasserIn] Faris, Pawan [verfasserIn] Pellavio, Giorgia [verfasserIn] Botta, Laura [verfasserIn] Orgiu, Matteo [verfasserIn] Forcaia, Greta [verfasserIn] Sancini, Giulio [verfasserIn] Laforenza, Umberto [verfasserIn] Moccia, Francesco [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2019 |
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| Schlagwörter: |
Brain microvascular endothelial cells |
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| Übergeordnetes Werk: |
Enthalten in: Cellular and molecular life sciences - Cham (ZG) : Springer International Publishing AG, 1997, 77(2019), 11 vom: 31. Aug., Seite 2235-2253 |
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| Übergeordnetes Werk: |
volume:77 ; year:2019 ; number:11 ; day:31 ; month:08 ; pages:2235-2253 |
| Links: |
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| DOI / URN: |
10.1007/s00018-019-03284-1 |
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| Katalog-ID: |
SPR039863646 |
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| 245 | 1 | 0 | |a Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular $ Ca^{2+} $ signals and nitric oxide release in human brain microvascular endothelial cells |
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| 520 | |a Abstract Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity causes an increase in local cerebral blood flow (CBF) to ensure local supply of oxygen and nutrients to the activated areas. The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-d-aspartate receptors to mediate extracellular $ Ca^{2+} $ entry and stimulate neuronal nitric oxide (NO) synthase to release NO, thereby triggering NVC. Recent work suggested that endothelial $ Ca^{2+} $ signals could underpin NVC by recruiting the endothelial NO synthase. For instance, acetylcholine induced intracellular $ Ca^{2+} $ signals followed by NO release by activating muscarinic 5 receptors in hCMEC/D3 cells, a widely employed model of human brain microvascular endothelial cells. Herein, we sought to assess whether also glutamate elicits metabotropic $ Ca^{2+} $ signals and NO release in hCMEC/D3 cells. Glutamate induced a dose-dependent increase in intracellular $ Ca^{2+} $ concentration ([$ Ca^{2+} $]i) that was blocked by α-methyl-4-carboxyphenylglycine and phenocopied by trans-1-amino-1,3-cyclopentanedicarboxylic acid, which, respectively, block and activate group 1 metabotropic glutamate receptors (mGluRs). Accordingly, hCMEC/D3 expressed both mGluR1 and mGluR5 and the $ Ca^{2+} $ response to glutamate was inhibited by their pharmacological blockade with, respectively, CPCCOEt and MTEP hydrochloride. The $ Ca^{2+} $ response to glutamate was initiated by endogenous $ Ca^{2+} $ release from the endoplasmic reticulum and endolysosomal $ Ca^{2+} $ store through inositol-1,4,5-trisphosphate receptors and two-pore channels, respectively, and sustained by store-operated $ Ca^{2+} $ entry. In addition, glutamate induced robust NO release that was suppressed by pharmacological blockade of the accompanying increase in [$ Ca^{2+} $]i. These data demonstrate for the first time that glutamate may induce metabotropic $ Ca^{2+} $ signals in human brain microvascular endothelial cells. The $ Ca^{2+} $ response to glutamate is likely to support NVC during neuronal activity, thereby reinforcing the emerging role of brain microvascular endothelial cells in the regulation of CBF. | ||
| 650 | 4 | |a Glutamate |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Neurovascular coupling |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Brain microvascular endothelial cells |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Group 1 metabotropic glutamate receptors |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Ca |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a signaling |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Nitric oxide |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Faris, Pawan |e verfasserin |4 aut | |
| 700 | 1 | |a Pellavio, Giorgia |e verfasserin |4 aut | |
| 700 | 1 | |a Botta, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Orgiu, Matteo |e verfasserin |4 aut | |
| 700 | 1 | |a Forcaia, Greta |e verfasserin |4 aut | |
| 700 | 1 | |a Sancini, Giulio |e verfasserin |4 aut | |
| 700 | 1 | |a Laforenza, Umberto |e verfasserin |4 aut | |
| 700 | 1 | |a Moccia, Francesco |e verfasserin |4 aut | |
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10.1007/s00018-019-03284-1 doi (DE-627)SPR039863646 (SPR)s00018-019-03284-1-e DE-627 ger DE-627 rakwb eng 570 610 ASE 42.15 bkl Negri, Sharon verfasserin aut Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular $ Ca^{2+} $ signals and nitric oxide release in human brain microvascular endothelial cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity causes an increase in local cerebral blood flow (CBF) to ensure local supply of oxygen and nutrients to the activated areas. The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-d-aspartate receptors to mediate extracellular $ Ca^{2+} $ entry and stimulate neuronal nitric oxide (NO) synthase to release NO, thereby triggering NVC. Recent work suggested that endothelial $ Ca^{2+} $ signals could underpin NVC by recruiting the endothelial NO synthase. For instance, acetylcholine induced intracellular $ Ca^{2+} $ signals followed by NO release by activating muscarinic 5 receptors in hCMEC/D3 cells, a widely employed model of human brain microvascular endothelial cells. Herein, we sought to assess whether also glutamate elicits metabotropic $ Ca^{2+} $ signals and NO release in hCMEC/D3 cells. Glutamate induced a dose-dependent increase in intracellular $ Ca^{2+} $ concentration ([$ Ca^{2+} $]i) that was blocked by α-methyl-4-carboxyphenylglycine and phenocopied by trans-1-amino-1,3-cyclopentanedicarboxylic acid, which, respectively, block and activate group 1 metabotropic glutamate receptors (mGluRs). Accordingly, hCMEC/D3 expressed both mGluR1 and mGluR5 and the $ Ca^{2+} $ response to glutamate was inhibited by their pharmacological blockade with, respectively, CPCCOEt and MTEP hydrochloride. The $ Ca^{2+} $ response to glutamate was initiated by endogenous $ Ca^{2+} $ release from the endoplasmic reticulum and endolysosomal $ Ca^{2+} $ store through inositol-1,4,5-trisphosphate receptors and two-pore channels, respectively, and sustained by store-operated $ Ca^{2+} $ entry. In addition, glutamate induced robust NO release that was suppressed by pharmacological blockade of the accompanying increase in [$ Ca^{2+} $]i. These data demonstrate for the first time that glutamate may induce metabotropic $ Ca^{2+} $ signals in human brain microvascular endothelial cells. The $ Ca^{2+} $ response to glutamate is likely to support NVC during neuronal activity, thereby reinforcing the emerging role of brain microvascular endothelial cells in the regulation of CBF. Glutamate (dpeaa)DE-He213 Neurovascular coupling (dpeaa)DE-He213 Brain microvascular endothelial cells (dpeaa)DE-He213 Group 1 metabotropic glutamate receptors (dpeaa)DE-He213 Ca (dpeaa)DE-He213 signaling (dpeaa)DE-He213 Nitric oxide (dpeaa)DE-He213 Faris, Pawan verfasserin aut Pellavio, Giorgia verfasserin aut Botta, Laura verfasserin aut Orgiu, Matteo verfasserin aut Forcaia, Greta verfasserin aut Sancini, Giulio verfasserin aut Laforenza, Umberto verfasserin aut Moccia, Francesco verfasserin aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 77(2019), 11 vom: 31. Aug., Seite 2235-2253 (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:77 year:2019 number:11 day:31 month:08 pages:2235-2253 https://dx.doi.org/10.1007/s00018-019-03284-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.15 ASE AR 77 2019 11 31 08 2235-2253 |
| spelling |
10.1007/s00018-019-03284-1 doi (DE-627)SPR039863646 (SPR)s00018-019-03284-1-e DE-627 ger DE-627 rakwb eng 570 610 ASE 42.15 bkl Negri, Sharon verfasserin aut Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular $ Ca^{2+} $ signals and nitric oxide release in human brain microvascular endothelial cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity causes an increase in local cerebral blood flow (CBF) to ensure local supply of oxygen and nutrients to the activated areas. The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-d-aspartate receptors to mediate extracellular $ Ca^{2+} $ entry and stimulate neuronal nitric oxide (NO) synthase to release NO, thereby triggering NVC. Recent work suggested that endothelial $ Ca^{2+} $ signals could underpin NVC by recruiting the endothelial NO synthase. For instance, acetylcholine induced intracellular $ Ca^{2+} $ signals followed by NO release by activating muscarinic 5 receptors in hCMEC/D3 cells, a widely employed model of human brain microvascular endothelial cells. Herein, we sought to assess whether also glutamate elicits metabotropic $ Ca^{2+} $ signals and NO release in hCMEC/D3 cells. Glutamate induced a dose-dependent increase in intracellular $ Ca^{2+} $ concentration ([$ Ca^{2+} $]i) that was blocked by α-methyl-4-carboxyphenylglycine and phenocopied by trans-1-amino-1,3-cyclopentanedicarboxylic acid, which, respectively, block and activate group 1 metabotropic glutamate receptors (mGluRs). Accordingly, hCMEC/D3 expressed both mGluR1 and mGluR5 and the $ Ca^{2+} $ response to glutamate was inhibited by their pharmacological blockade with, respectively, CPCCOEt and MTEP hydrochloride. The $ Ca^{2+} $ response to glutamate was initiated by endogenous $ Ca^{2+} $ release from the endoplasmic reticulum and endolysosomal $ Ca^{2+} $ store through inositol-1,4,5-trisphosphate receptors and two-pore channels, respectively, and sustained by store-operated $ Ca^{2+} $ entry. In addition, glutamate induced robust NO release that was suppressed by pharmacological blockade of the accompanying increase in [$ Ca^{2+} $]i. These data demonstrate for the first time that glutamate may induce metabotropic $ Ca^{2+} $ signals in human brain microvascular endothelial cells. The $ Ca^{2+} $ response to glutamate is likely to support NVC during neuronal activity, thereby reinforcing the emerging role of brain microvascular endothelial cells in the regulation of CBF. Glutamate (dpeaa)DE-He213 Neurovascular coupling (dpeaa)DE-He213 Brain microvascular endothelial cells (dpeaa)DE-He213 Group 1 metabotropic glutamate receptors (dpeaa)DE-He213 Ca (dpeaa)DE-He213 signaling (dpeaa)DE-He213 Nitric oxide (dpeaa)DE-He213 Faris, Pawan verfasserin aut Pellavio, Giorgia verfasserin aut Botta, Laura verfasserin aut Orgiu, Matteo verfasserin aut Forcaia, Greta verfasserin aut Sancini, Giulio verfasserin aut Laforenza, Umberto verfasserin aut Moccia, Francesco verfasserin aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 77(2019), 11 vom: 31. Aug., Seite 2235-2253 (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:77 year:2019 number:11 day:31 month:08 pages:2235-2253 https://dx.doi.org/10.1007/s00018-019-03284-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.15 ASE AR 77 2019 11 31 08 2235-2253 |
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10.1007/s00018-019-03284-1 doi (DE-627)SPR039863646 (SPR)s00018-019-03284-1-e DE-627 ger DE-627 rakwb eng 570 610 ASE 42.15 bkl Negri, Sharon verfasserin aut Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular $ Ca^{2+} $ signals and nitric oxide release in human brain microvascular endothelial cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity causes an increase in local cerebral blood flow (CBF) to ensure local supply of oxygen and nutrients to the activated areas. The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-d-aspartate receptors to mediate extracellular $ Ca^{2+} $ entry and stimulate neuronal nitric oxide (NO) synthase to release NO, thereby triggering NVC. Recent work suggested that endothelial $ Ca^{2+} $ signals could underpin NVC by recruiting the endothelial NO synthase. For instance, acetylcholine induced intracellular $ Ca^{2+} $ signals followed by NO release by activating muscarinic 5 receptors in hCMEC/D3 cells, a widely employed model of human brain microvascular endothelial cells. Herein, we sought to assess whether also glutamate elicits metabotropic $ Ca^{2+} $ signals and NO release in hCMEC/D3 cells. Glutamate induced a dose-dependent increase in intracellular $ Ca^{2+} $ concentration ([$ Ca^{2+} $]i) that was blocked by α-methyl-4-carboxyphenylglycine and phenocopied by trans-1-amino-1,3-cyclopentanedicarboxylic acid, which, respectively, block and activate group 1 metabotropic glutamate receptors (mGluRs). Accordingly, hCMEC/D3 expressed both mGluR1 and mGluR5 and the $ Ca^{2+} $ response to glutamate was inhibited by their pharmacological blockade with, respectively, CPCCOEt and MTEP hydrochloride. The $ Ca^{2+} $ response to glutamate was initiated by endogenous $ Ca^{2+} $ release from the endoplasmic reticulum and endolysosomal $ Ca^{2+} $ store through inositol-1,4,5-trisphosphate receptors and two-pore channels, respectively, and sustained by store-operated $ Ca^{2+} $ entry. In addition, glutamate induced robust NO release that was suppressed by pharmacological blockade of the accompanying increase in [$ Ca^{2+} $]i. These data demonstrate for the first time that glutamate may induce metabotropic $ Ca^{2+} $ signals in human brain microvascular endothelial cells. The $ Ca^{2+} $ response to glutamate is likely to support NVC during neuronal activity, thereby reinforcing the emerging role of brain microvascular endothelial cells in the regulation of CBF. Glutamate (dpeaa)DE-He213 Neurovascular coupling (dpeaa)DE-He213 Brain microvascular endothelial cells (dpeaa)DE-He213 Group 1 metabotropic glutamate receptors (dpeaa)DE-He213 Ca (dpeaa)DE-He213 signaling (dpeaa)DE-He213 Nitric oxide (dpeaa)DE-He213 Faris, Pawan verfasserin aut Pellavio, Giorgia verfasserin aut Botta, Laura verfasserin aut Orgiu, Matteo verfasserin aut Forcaia, Greta verfasserin aut Sancini, Giulio verfasserin aut Laforenza, Umberto verfasserin aut Moccia, Francesco verfasserin aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 77(2019), 11 vom: 31. Aug., Seite 2235-2253 (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:77 year:2019 number:11 day:31 month:08 pages:2235-2253 https://dx.doi.org/10.1007/s00018-019-03284-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.15 ASE AR 77 2019 11 31 08 2235-2253 |
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10.1007/s00018-019-03284-1 doi (DE-627)SPR039863646 (SPR)s00018-019-03284-1-e DE-627 ger DE-627 rakwb eng 570 610 ASE 42.15 bkl Negri, Sharon verfasserin aut Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular $ Ca^{2+} $ signals and nitric oxide release in human brain microvascular endothelial cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity causes an increase in local cerebral blood flow (CBF) to ensure local supply of oxygen and nutrients to the activated areas. The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-d-aspartate receptors to mediate extracellular $ Ca^{2+} $ entry and stimulate neuronal nitric oxide (NO) synthase to release NO, thereby triggering NVC. Recent work suggested that endothelial $ Ca^{2+} $ signals could underpin NVC by recruiting the endothelial NO synthase. For instance, acetylcholine induced intracellular $ Ca^{2+} $ signals followed by NO release by activating muscarinic 5 receptors in hCMEC/D3 cells, a widely employed model of human brain microvascular endothelial cells. Herein, we sought to assess whether also glutamate elicits metabotropic $ Ca^{2+} $ signals and NO release in hCMEC/D3 cells. Glutamate induced a dose-dependent increase in intracellular $ Ca^{2+} $ concentration ([$ Ca^{2+} $]i) that was blocked by α-methyl-4-carboxyphenylglycine and phenocopied by trans-1-amino-1,3-cyclopentanedicarboxylic acid, which, respectively, block and activate group 1 metabotropic glutamate receptors (mGluRs). Accordingly, hCMEC/D3 expressed both mGluR1 and mGluR5 and the $ Ca^{2+} $ response to glutamate was inhibited by their pharmacological blockade with, respectively, CPCCOEt and MTEP hydrochloride. The $ Ca^{2+} $ response to glutamate was initiated by endogenous $ Ca^{2+} $ release from the endoplasmic reticulum and endolysosomal $ Ca^{2+} $ store through inositol-1,4,5-trisphosphate receptors and two-pore channels, respectively, and sustained by store-operated $ Ca^{2+} $ entry. In addition, glutamate induced robust NO release that was suppressed by pharmacological blockade of the accompanying increase in [$ Ca^{2+} $]i. These data demonstrate for the first time that glutamate may induce metabotropic $ Ca^{2+} $ signals in human brain microvascular endothelial cells. The $ Ca^{2+} $ response to glutamate is likely to support NVC during neuronal activity, thereby reinforcing the emerging role of brain microvascular endothelial cells in the regulation of CBF. Glutamate (dpeaa)DE-He213 Neurovascular coupling (dpeaa)DE-He213 Brain microvascular endothelial cells (dpeaa)DE-He213 Group 1 metabotropic glutamate receptors (dpeaa)DE-He213 Ca (dpeaa)DE-He213 signaling (dpeaa)DE-He213 Nitric oxide (dpeaa)DE-He213 Faris, Pawan verfasserin aut Pellavio, Giorgia verfasserin aut Botta, Laura verfasserin aut Orgiu, Matteo verfasserin aut Forcaia, Greta verfasserin aut Sancini, Giulio verfasserin aut Laforenza, Umberto verfasserin aut Moccia, Francesco verfasserin aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 77(2019), 11 vom: 31. Aug., Seite 2235-2253 (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:77 year:2019 number:11 day:31 month:08 pages:2235-2253 https://dx.doi.org/10.1007/s00018-019-03284-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.15 ASE AR 77 2019 11 31 08 2235-2253 |
| allfieldsSound |
10.1007/s00018-019-03284-1 doi (DE-627)SPR039863646 (SPR)s00018-019-03284-1-e DE-627 ger DE-627 rakwb eng 570 610 ASE 42.15 bkl Negri, Sharon verfasserin aut Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular $ Ca^{2+} $ signals and nitric oxide release in human brain microvascular endothelial cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity causes an increase in local cerebral blood flow (CBF) to ensure local supply of oxygen and nutrients to the activated areas. The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-d-aspartate receptors to mediate extracellular $ Ca^{2+} $ entry and stimulate neuronal nitric oxide (NO) synthase to release NO, thereby triggering NVC. Recent work suggested that endothelial $ Ca^{2+} $ signals could underpin NVC by recruiting the endothelial NO synthase. For instance, acetylcholine induced intracellular $ Ca^{2+} $ signals followed by NO release by activating muscarinic 5 receptors in hCMEC/D3 cells, a widely employed model of human brain microvascular endothelial cells. Herein, we sought to assess whether also glutamate elicits metabotropic $ Ca^{2+} $ signals and NO release in hCMEC/D3 cells. Glutamate induced a dose-dependent increase in intracellular $ Ca^{2+} $ concentration ([$ Ca^{2+} $]i) that was blocked by α-methyl-4-carboxyphenylglycine and phenocopied by trans-1-amino-1,3-cyclopentanedicarboxylic acid, which, respectively, block and activate group 1 metabotropic glutamate receptors (mGluRs). Accordingly, hCMEC/D3 expressed both mGluR1 and mGluR5 and the $ Ca^{2+} $ response to glutamate was inhibited by their pharmacological blockade with, respectively, CPCCOEt and MTEP hydrochloride. The $ Ca^{2+} $ response to glutamate was initiated by endogenous $ Ca^{2+} $ release from the endoplasmic reticulum and endolysosomal $ Ca^{2+} $ store through inositol-1,4,5-trisphosphate receptors and two-pore channels, respectively, and sustained by store-operated $ Ca^{2+} $ entry. In addition, glutamate induced robust NO release that was suppressed by pharmacological blockade of the accompanying increase in [$ Ca^{2+} $]i. These data demonstrate for the first time that glutamate may induce metabotropic $ Ca^{2+} $ signals in human brain microvascular endothelial cells. The $ Ca^{2+} $ response to glutamate is likely to support NVC during neuronal activity, thereby reinforcing the emerging role of brain microvascular endothelial cells in the regulation of CBF. Glutamate (dpeaa)DE-He213 Neurovascular coupling (dpeaa)DE-He213 Brain microvascular endothelial cells (dpeaa)DE-He213 Group 1 metabotropic glutamate receptors (dpeaa)DE-He213 Ca (dpeaa)DE-He213 signaling (dpeaa)DE-He213 Nitric oxide (dpeaa)DE-He213 Faris, Pawan verfasserin aut Pellavio, Giorgia verfasserin aut Botta, Laura verfasserin aut Orgiu, Matteo verfasserin aut Forcaia, Greta verfasserin aut Sancini, Giulio verfasserin aut Laforenza, Umberto verfasserin aut Moccia, Francesco verfasserin aut Enthalten in Cellular and molecular life sciences Cham (ZG) : Springer International Publishing AG, 1997 77(2019), 11 vom: 31. Aug., Seite 2235-2253 (DE-627)253390524 (DE-600)1458497-9 1420-9071 nnns volume:77 year:2019 number:11 day:31 month:08 pages:2235-2253 https://dx.doi.org/10.1007/s00018-019-03284-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 42.15 ASE AR 77 2019 11 31 08 2235-2253 |
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English |
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Enthalten in Cellular and molecular life sciences 77(2019), 11 vom: 31. Aug., Seite 2235-2253 volume:77 year:2019 number:11 day:31 month:08 pages:2235-2253 |
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Enthalten in Cellular and molecular life sciences 77(2019), 11 vom: 31. Aug., Seite 2235-2253 volume:77 year:2019 number:11 day:31 month:08 pages:2235-2253 |
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Glutamate Neurovascular coupling Brain microvascular endothelial cells Group 1 metabotropic glutamate receptors Ca signaling Nitric oxide |
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Negri, Sharon @@aut@@ Faris, Pawan @@aut@@ Pellavio, Giorgia @@aut@@ Botta, Laura @@aut@@ Orgiu, Matteo @@aut@@ Forcaia, Greta @@aut@@ Sancini, Giulio @@aut@@ Laforenza, Umberto @@aut@@ Moccia, Francesco @@aut@@ |
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2019-08-31T00:00:00Z |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR039863646</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519171958.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2019 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s00018-019-03284-1</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR039863646</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s00018-019-03284-1-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">42.15</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Negri, Sharon</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular $ Ca^{2+} $ signals and nitric oxide release in human brain microvascular endothelial cells</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity causes an increase in local cerebral blood flow (CBF) to ensure local supply of oxygen and nutrients to the activated areas. The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-d-aspartate receptors to mediate extracellular $ Ca^{2+} $ entry and stimulate neuronal nitric oxide (NO) synthase to release NO, thereby triggering NVC. Recent work suggested that endothelial $ Ca^{2+} $ signals could underpin NVC by recruiting the endothelial NO synthase. For instance, acetylcholine induced intracellular $ Ca^{2+} $ signals followed by NO release by activating muscarinic 5 receptors in hCMEC/D3 cells, a widely employed model of human brain microvascular endothelial cells. Herein, we sought to assess whether also glutamate elicits metabotropic $ Ca^{2+} $ signals and NO release in hCMEC/D3 cells. Glutamate induced a dose-dependent increase in intracellular $ Ca^{2+} $ concentration ([$ Ca^{2+} $]i) that was blocked by α-methyl-4-carboxyphenylglycine and phenocopied by trans-1-amino-1,3-cyclopentanedicarboxylic acid, which, respectively, block and activate group 1 metabotropic glutamate receptors (mGluRs). Accordingly, hCMEC/D3 expressed both mGluR1 and mGluR5 and the $ Ca^{2+} $ response to glutamate was inhibited by their pharmacological blockade with, respectively, CPCCOEt and MTEP hydrochloride. The $ Ca^{2+} $ response to glutamate was initiated by endogenous $ Ca^{2+} $ release from the endoplasmic reticulum and endolysosomal $ Ca^{2+} $ store through inositol-1,4,5-trisphosphate receptors and two-pore channels, respectively, and sustained by store-operated $ Ca^{2+} $ entry. In addition, glutamate induced robust NO release that was suppressed by pharmacological blockade of the accompanying increase in [$ Ca^{2+} $]i. These data demonstrate for the first time that glutamate may induce metabotropic $ Ca^{2+} $ signals in human brain microvascular endothelial cells. 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|
| author |
Negri, Sharon |
| spellingShingle |
Negri, Sharon ddc 570 bkl 42.15 misc Glutamate misc Neurovascular coupling misc Brain microvascular endothelial cells misc Group 1 metabotropic glutamate receptors misc Ca misc signaling misc Nitric oxide Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular $ Ca^{2+} $ signals and nitric oxide release in human brain microvascular endothelial cells |
| authorStr |
Negri, Sharon |
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@@773@@(DE-627)253390524 |
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electronic Article |
| dewey-ones |
570 - Life sciences; biology 610 - Medicine & health |
| delete_txt_mv |
keep |
| author_role |
aut aut aut aut aut aut aut aut aut |
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springer |
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true |
| illustrated |
Not Illustrated |
| issn |
1420-9071 |
| topic_title |
570 610 ASE 42.15 bkl Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular $ Ca^{2+} $ signals and nitric oxide release in human brain microvascular endothelial cells Glutamate (dpeaa)DE-He213 Neurovascular coupling (dpeaa)DE-He213 Brain microvascular endothelial cells (dpeaa)DE-He213 Group 1 metabotropic glutamate receptors (dpeaa)DE-He213 Ca (dpeaa)DE-He213 signaling (dpeaa)DE-He213 Nitric oxide (dpeaa)DE-He213 |
| topic |
ddc 570 bkl 42.15 misc Glutamate misc Neurovascular coupling misc Brain microvascular endothelial cells misc Group 1 metabotropic glutamate receptors misc Ca misc signaling misc Nitric oxide |
| topic_unstemmed |
ddc 570 bkl 42.15 misc Glutamate misc Neurovascular coupling misc Brain microvascular endothelial cells misc Group 1 metabotropic glutamate receptors misc Ca misc signaling misc Nitric oxide |
| topic_browse |
ddc 570 bkl 42.15 misc Glutamate misc Neurovascular coupling misc Brain microvascular endothelial cells misc Group 1 metabotropic glutamate receptors misc Ca misc signaling misc Nitric oxide |
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Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular $ Ca^{2+} $ signals and nitric oxide release in human brain microvascular endothelial cells |
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Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular $ Ca^{2+} $ signals and nitric oxide release in human brain microvascular endothelial cells |
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Negri, Sharon |
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Cellular and molecular life sciences |
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Negri, Sharon Faris, Pawan Pellavio, Giorgia Botta, Laura Orgiu, Matteo Forcaia, Greta Sancini, Giulio Laforenza, Umberto Moccia, Francesco |
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group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular $ ca^{2+} $ signals and nitric oxide release in human brain microvascular endothelial cells |
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Group 1 metabotropic glutamate receptors trigger glutamate-induced intracellular $ Ca^{2+} $ signals and nitric oxide release in human brain microvascular endothelial cells |
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Abstract Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity causes an increase in local cerebral blood flow (CBF) to ensure local supply of oxygen and nutrients to the activated areas. The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-d-aspartate receptors to mediate extracellular $ Ca^{2+} $ entry and stimulate neuronal nitric oxide (NO) synthase to release NO, thereby triggering NVC. Recent work suggested that endothelial $ Ca^{2+} $ signals could underpin NVC by recruiting the endothelial NO synthase. For instance, acetylcholine induced intracellular $ Ca^{2+} $ signals followed by NO release by activating muscarinic 5 receptors in hCMEC/D3 cells, a widely employed model of human brain microvascular endothelial cells. Herein, we sought to assess whether also glutamate elicits metabotropic $ Ca^{2+} $ signals and NO release in hCMEC/D3 cells. Glutamate induced a dose-dependent increase in intracellular $ Ca^{2+} $ concentration ([$ Ca^{2+} $]i) that was blocked by α-methyl-4-carboxyphenylglycine and phenocopied by trans-1-amino-1,3-cyclopentanedicarboxylic acid, which, respectively, block and activate group 1 metabotropic glutamate receptors (mGluRs). Accordingly, hCMEC/D3 expressed both mGluR1 and mGluR5 and the $ Ca^{2+} $ response to glutamate was inhibited by their pharmacological blockade with, respectively, CPCCOEt and MTEP hydrochloride. The $ Ca^{2+} $ response to glutamate was initiated by endogenous $ Ca^{2+} $ release from the endoplasmic reticulum and endolysosomal $ Ca^{2+} $ store through inositol-1,4,5-trisphosphate receptors and two-pore channels, respectively, and sustained by store-operated $ Ca^{2+} $ entry. In addition, glutamate induced robust NO release that was suppressed by pharmacological blockade of the accompanying increase in [$ Ca^{2+} $]i. These data demonstrate for the first time that glutamate may induce metabotropic $ Ca^{2+} $ signals in human brain microvascular endothelial cells. The $ Ca^{2+} $ response to glutamate is likely to support NVC during neuronal activity, thereby reinforcing the emerging role of brain microvascular endothelial cells in the regulation of CBF. |
| abstractGer |
Abstract Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity causes an increase in local cerebral blood flow (CBF) to ensure local supply of oxygen and nutrients to the activated areas. The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-d-aspartate receptors to mediate extracellular $ Ca^{2+} $ entry and stimulate neuronal nitric oxide (NO) synthase to release NO, thereby triggering NVC. Recent work suggested that endothelial $ Ca^{2+} $ signals could underpin NVC by recruiting the endothelial NO synthase. For instance, acetylcholine induced intracellular $ Ca^{2+} $ signals followed by NO release by activating muscarinic 5 receptors in hCMEC/D3 cells, a widely employed model of human brain microvascular endothelial cells. Herein, we sought to assess whether also glutamate elicits metabotropic $ Ca^{2+} $ signals and NO release in hCMEC/D3 cells. Glutamate induced a dose-dependent increase in intracellular $ Ca^{2+} $ concentration ([$ Ca^{2+} $]i) that was blocked by α-methyl-4-carboxyphenylglycine and phenocopied by trans-1-amino-1,3-cyclopentanedicarboxylic acid, which, respectively, block and activate group 1 metabotropic glutamate receptors (mGluRs). Accordingly, hCMEC/D3 expressed both mGluR1 and mGluR5 and the $ Ca^{2+} $ response to glutamate was inhibited by their pharmacological blockade with, respectively, CPCCOEt and MTEP hydrochloride. The $ Ca^{2+} $ response to glutamate was initiated by endogenous $ Ca^{2+} $ release from the endoplasmic reticulum and endolysosomal $ Ca^{2+} $ store through inositol-1,4,5-trisphosphate receptors and two-pore channels, respectively, and sustained by store-operated $ Ca^{2+} $ entry. In addition, glutamate induced robust NO release that was suppressed by pharmacological blockade of the accompanying increase in [$ Ca^{2+} $]i. These data demonstrate for the first time that glutamate may induce metabotropic $ Ca^{2+} $ signals in human brain microvascular endothelial cells. The $ Ca^{2+} $ response to glutamate is likely to support NVC during neuronal activity, thereby reinforcing the emerging role of brain microvascular endothelial cells in the regulation of CBF. |
| abstract_unstemmed |
Abstract Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity causes an increase in local cerebral blood flow (CBF) to ensure local supply of oxygen and nutrients to the activated areas. The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-d-aspartate receptors to mediate extracellular $ Ca^{2+} $ entry and stimulate neuronal nitric oxide (NO) synthase to release NO, thereby triggering NVC. Recent work suggested that endothelial $ Ca^{2+} $ signals could underpin NVC by recruiting the endothelial NO synthase. For instance, acetylcholine induced intracellular $ Ca^{2+} $ signals followed by NO release by activating muscarinic 5 receptors in hCMEC/D3 cells, a widely employed model of human brain microvascular endothelial cells. Herein, we sought to assess whether also glutamate elicits metabotropic $ Ca^{2+} $ signals and NO release in hCMEC/D3 cells. Glutamate induced a dose-dependent increase in intracellular $ Ca^{2+} $ concentration ([$ Ca^{2+} $]i) that was blocked by α-methyl-4-carboxyphenylglycine and phenocopied by trans-1-amino-1,3-cyclopentanedicarboxylic acid, which, respectively, block and activate group 1 metabotropic glutamate receptors (mGluRs). Accordingly, hCMEC/D3 expressed both mGluR1 and mGluR5 and the $ Ca^{2+} $ response to glutamate was inhibited by their pharmacological blockade with, respectively, CPCCOEt and MTEP hydrochloride. The $ Ca^{2+} $ response to glutamate was initiated by endogenous $ Ca^{2+} $ release from the endoplasmic reticulum and endolysosomal $ Ca^{2+} $ store through inositol-1,4,5-trisphosphate receptors and two-pore channels, respectively, and sustained by store-operated $ Ca^{2+} $ entry. In addition, glutamate induced robust NO release that was suppressed by pharmacological blockade of the accompanying increase in [$ Ca^{2+} $]i. These data demonstrate for the first time that glutamate may induce metabotropic $ Ca^{2+} $ signals in human brain microvascular endothelial cells. The $ Ca^{2+} $ response to glutamate is likely to support NVC during neuronal activity, thereby reinforcing the emerging role of brain microvascular endothelial cells in the regulation of CBF. |
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| score |
7.401908 |