Interactions between Glycine and Glutamate through Activation of Their Transporters in Hippocampal Nerve Terminals

Evidence supports the pathophysiological relevance of crosstalk between the neurotransmitters Glycine and Glutamate and their close interactions; some reports even support the possibility of Glycine–Glutamate cotransmission in central nervous system (CNS) areas, including the hippocampus. Functional studies with isolated nerve terminals (synaptosomes) permit us to study transporter-mediated interactions between neurotransmitters that lead to the regulation of transmitter release. Our main aims here were: (i) to investigate release-regulating, transporter-mediated interactions between Glycine and Glutamate in hippocampal nerve terminals and (ii) to determine the coexistence of transporters for Glycine and Glutamate in these terminals. Purified synaptosomes, analyzed at the ultrastructural level via electron microscopy, were used as the experimental model. Mouse hippocampal synaptosomes were prelabeled with [<sup<3</sup<H]D-Aspartate or [<sup<3</sup<H]Glycine; the release of radiolabeled tracers was monitored with the superfusion technique. The main findings were that (i) exogenous Glycine stimulated [<sup<3</sup<H]D-Aspartate release, partly by activation of GlyT1 and in part, unusually, through GlyT2 transporters and that (ii) D-Aspartate stimulated [<sup<3</sup<H]glycine release by a process that was sensitive to Glutamate transporter blockers. Based on the features of the experimental model used, it is suggested that functional transporters for Glutamate and Glycine coexist in a small subset of hippocampal nerve terminals, a condition that may also be compatible with cotransmission; glycinergic and glutamatergic transporters exhibit different functions and mediate interactions between the neurotransmitters. It is hoped that increased information on Glutamate–Glycine interactions in different areas, including the hippocampus, will contribute to a better knowledge of drugs acting at “glycinergic” targets, currently under study in relation with different CNS pathologies. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Katia Cortese [verfasserIn] Maria Cristina Gagliani [verfasserIn] Luca Raiteri [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	glycine release glutamate release NMDA receptors glycine transporter 1 (GlyT1) glycine transporter 2 (GlyT2) EAAT transporters

Übergeordnetes Werk:	In: Biomedicines - MDPI AG, 2014, 11(2023), 12, p 3152
Übergeordnetes Werk:	volume:11 ; year:2023 ; number:12, p 3152

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/biomedicines11123152

Katalog-ID:	DOAJ098908030

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allfields	10.3390/biomedicines11123152 doi (DE-627)DOAJ098908030 (DE-599)DOAJ1fdfd39405184f4b9a57e0a69246463c DE-627 ger DE-627 rakwb eng QH301-705.5 Katia Cortese verfasserin aut Interactions between Glycine and Glutamate through Activation of Their Transporters in Hippocampal Nerve Terminals 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Evidence supports the pathophysiological relevance of crosstalk between the neurotransmitters Glycine and Glutamate and their close interactions; some reports even support the possibility of Glycine–Glutamate cotransmission in central nervous system (CNS) areas, including the hippocampus. Functional studies with isolated nerve terminals (synaptosomes) permit us to study transporter-mediated interactions between neurotransmitters that lead to the regulation of transmitter release. Our main aims here were: (i) to investigate release-regulating, transporter-mediated interactions between Glycine and Glutamate in hippocampal nerve terminals and (ii) to determine the coexistence of transporters for Glycine and Glutamate in these terminals. Purified synaptosomes, analyzed at the ultrastructural level via electron microscopy, were used as the experimental model. Mouse hippocampal synaptosomes were prelabeled with [<sup<3</sup<H]D-Aspartate or [<sup<3</sup<H]Glycine; the release of radiolabeled tracers was monitored with the superfusion technique. The main findings were that (i) exogenous Glycine stimulated [<sup<3</sup<H]D-Aspartate release, partly by activation of GlyT1 and in part, unusually, through GlyT2 transporters and that (ii) D-Aspartate stimulated [<sup<3</sup<H]glycine release by a process that was sensitive to Glutamate transporter blockers. Based on the features of the experimental model used, it is suggested that functional transporters for Glutamate and Glycine coexist in a small subset of hippocampal nerve terminals, a condition that may also be compatible with cotransmission; glycinergic and glutamatergic transporters exhibit different functions and mediate interactions between the neurotransmitters. It is hoped that increased information on Glutamate–Glycine interactions in different areas, including the hippocampus, will contribute to a better knowledge of drugs acting at “glycinergic” targets, currently under study in relation with different CNS pathologies. glycine release glutamate release NMDA receptors glycine transporter 1 (GlyT1) glycine transporter 2 (GlyT2) EAAT transporters Biology (General) Maria Cristina Gagliani verfasserin aut Luca Raiteri verfasserin aut In Biomedicines MDPI AG, 2014 11(2023), 12, p 3152 (DE-627)750370483 (DE-600)2720867-9 22279059 nnns volume:11 year:2023 number:12, p 3152 https://doi.org/10.3390/biomedicines11123152 kostenfrei https://doaj.org/article/1fdfd39405184f4b9a57e0a69246463c kostenfrei https://www.mdpi.com/2227-9059/11/12/3152 kostenfrei https://doaj.org/toc/2227-9059 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 12, p 3152
spelling	10.3390/biomedicines11123152 doi (DE-627)DOAJ098908030 (DE-599)DOAJ1fdfd39405184f4b9a57e0a69246463c DE-627 ger DE-627 rakwb eng QH301-705.5 Katia Cortese verfasserin aut Interactions between Glycine and Glutamate through Activation of Their Transporters in Hippocampal Nerve Terminals 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Evidence supports the pathophysiological relevance of crosstalk between the neurotransmitters Glycine and Glutamate and their close interactions; some reports even support the possibility of Glycine–Glutamate cotransmission in central nervous system (CNS) areas, including the hippocampus. Functional studies with isolated nerve terminals (synaptosomes) permit us to study transporter-mediated interactions between neurotransmitters that lead to the regulation of transmitter release. Our main aims here were: (i) to investigate release-regulating, transporter-mediated interactions between Glycine and Glutamate in hippocampal nerve terminals and (ii) to determine the coexistence of transporters for Glycine and Glutamate in these terminals. Purified synaptosomes, analyzed at the ultrastructural level via electron microscopy, were used as the experimental model. Mouse hippocampal synaptosomes were prelabeled with [<sup<3</sup<H]D-Aspartate or [<sup<3</sup<H]Glycine; the release of radiolabeled tracers was monitored with the superfusion technique. The main findings were that (i) exogenous Glycine stimulated [<sup<3</sup<H]D-Aspartate release, partly by activation of GlyT1 and in part, unusually, through GlyT2 transporters and that (ii) D-Aspartate stimulated [<sup<3</sup<H]glycine release by a process that was sensitive to Glutamate transporter blockers. Based on the features of the experimental model used, it is suggested that functional transporters for Glutamate and Glycine coexist in a small subset of hippocampal nerve terminals, a condition that may also be compatible with cotransmission; glycinergic and glutamatergic transporters exhibit different functions and mediate interactions between the neurotransmitters. It is hoped that increased information on Glutamate–Glycine interactions in different areas, including the hippocampus, will contribute to a better knowledge of drugs acting at “glycinergic” targets, currently under study in relation with different CNS pathologies. glycine release glutamate release NMDA receptors glycine transporter 1 (GlyT1) glycine transporter 2 (GlyT2) EAAT transporters Biology (General) Maria Cristina Gagliani verfasserin aut Luca Raiteri verfasserin aut In Biomedicines MDPI AG, 2014 11(2023), 12, p 3152 (DE-627)750370483 (DE-600)2720867-9 22279059 nnns volume:11 year:2023 number:12, p 3152 https://doi.org/10.3390/biomedicines11123152 kostenfrei https://doaj.org/article/1fdfd39405184f4b9a57e0a69246463c kostenfrei https://www.mdpi.com/2227-9059/11/12/3152 kostenfrei https://doaj.org/toc/2227-9059 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 12, p 3152
allfields_unstemmed	10.3390/biomedicines11123152 doi (DE-627)DOAJ098908030 (DE-599)DOAJ1fdfd39405184f4b9a57e0a69246463c DE-627 ger DE-627 rakwb eng QH301-705.5 Katia Cortese verfasserin aut Interactions between Glycine and Glutamate through Activation of Their Transporters in Hippocampal Nerve Terminals 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Evidence supports the pathophysiological relevance of crosstalk between the neurotransmitters Glycine and Glutamate and their close interactions; some reports even support the possibility of Glycine–Glutamate cotransmission in central nervous system (CNS) areas, including the hippocampus. Functional studies with isolated nerve terminals (synaptosomes) permit us to study transporter-mediated interactions between neurotransmitters that lead to the regulation of transmitter release. Our main aims here were: (i) to investigate release-regulating, transporter-mediated interactions between Glycine and Glutamate in hippocampal nerve terminals and (ii) to determine the coexistence of transporters for Glycine and Glutamate in these terminals. Purified synaptosomes, analyzed at the ultrastructural level via electron microscopy, were used as the experimental model. Mouse hippocampal synaptosomes were prelabeled with [<sup<3</sup<H]D-Aspartate or [<sup<3</sup<H]Glycine; the release of radiolabeled tracers was monitored with the superfusion technique. The main findings were that (i) exogenous Glycine stimulated [<sup<3</sup<H]D-Aspartate release, partly by activation of GlyT1 and in part, unusually, through GlyT2 transporters and that (ii) D-Aspartate stimulated [<sup<3</sup<H]glycine release by a process that was sensitive to Glutamate transporter blockers. Based on the features of the experimental model used, it is suggested that functional transporters for Glutamate and Glycine coexist in a small subset of hippocampal nerve terminals, a condition that may also be compatible with cotransmission; glycinergic and glutamatergic transporters exhibit different functions and mediate interactions between the neurotransmitters. It is hoped that increased information on Glutamate–Glycine interactions in different areas, including the hippocampus, will contribute to a better knowledge of drugs acting at “glycinergic” targets, currently under study in relation with different CNS pathologies. glycine release glutamate release NMDA receptors glycine transporter 1 (GlyT1) glycine transporter 2 (GlyT2) EAAT transporters Biology (General) Maria Cristina Gagliani verfasserin aut Luca Raiteri verfasserin aut In Biomedicines MDPI AG, 2014 11(2023), 12, p 3152 (DE-627)750370483 (DE-600)2720867-9 22279059 nnns volume:11 year:2023 number:12, p 3152 https://doi.org/10.3390/biomedicines11123152 kostenfrei https://doaj.org/article/1fdfd39405184f4b9a57e0a69246463c kostenfrei https://www.mdpi.com/2227-9059/11/12/3152 kostenfrei https://doaj.org/toc/2227-9059 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 12, p 3152
allfieldsGer	10.3390/biomedicines11123152 doi (DE-627)DOAJ098908030 (DE-599)DOAJ1fdfd39405184f4b9a57e0a69246463c DE-627 ger DE-627 rakwb eng QH301-705.5 Katia Cortese verfasserin aut Interactions between Glycine and Glutamate through Activation of Their Transporters in Hippocampal Nerve Terminals 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Evidence supports the pathophysiological relevance of crosstalk between the neurotransmitters Glycine and Glutamate and their close interactions; some reports even support the possibility of Glycine–Glutamate cotransmission in central nervous system (CNS) areas, including the hippocampus. Functional studies with isolated nerve terminals (synaptosomes) permit us to study transporter-mediated interactions between neurotransmitters that lead to the regulation of transmitter release. Our main aims here were: (i) to investigate release-regulating, transporter-mediated interactions between Glycine and Glutamate in hippocampal nerve terminals and (ii) to determine the coexistence of transporters for Glycine and Glutamate in these terminals. Purified synaptosomes, analyzed at the ultrastructural level via electron microscopy, were used as the experimental model. Mouse hippocampal synaptosomes were prelabeled with [<sup<3</sup<H]D-Aspartate or [<sup<3</sup<H]Glycine; the release of radiolabeled tracers was monitored with the superfusion technique. The main findings were that (i) exogenous Glycine stimulated [<sup<3</sup<H]D-Aspartate release, partly by activation of GlyT1 and in part, unusually, through GlyT2 transporters and that (ii) D-Aspartate stimulated [<sup<3</sup<H]glycine release by a process that was sensitive to Glutamate transporter blockers. Based on the features of the experimental model used, it is suggested that functional transporters for Glutamate and Glycine coexist in a small subset of hippocampal nerve terminals, a condition that may also be compatible with cotransmission; glycinergic and glutamatergic transporters exhibit different functions and mediate interactions between the neurotransmitters. It is hoped that increased information on Glutamate–Glycine interactions in different areas, including the hippocampus, will contribute to a better knowledge of drugs acting at “glycinergic” targets, currently under study in relation with different CNS pathologies. glycine release glutamate release NMDA receptors glycine transporter 1 (GlyT1) glycine transporter 2 (GlyT2) EAAT transporters Biology (General) Maria Cristina Gagliani verfasserin aut Luca Raiteri verfasserin aut In Biomedicines MDPI AG, 2014 11(2023), 12, p 3152 (DE-627)750370483 (DE-600)2720867-9 22279059 nnns volume:11 year:2023 number:12, p 3152 https://doi.org/10.3390/biomedicines11123152 kostenfrei https://doaj.org/article/1fdfd39405184f4b9a57e0a69246463c kostenfrei https://www.mdpi.com/2227-9059/11/12/3152 kostenfrei https://doaj.org/toc/2227-9059 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 12, p 3152
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author-letter	Katia Cortese
doi_str_mv	10.3390/biomedicines11123152
author2-role	verfasserin
title_sort	interactions between glycine and glutamate through activation of their transporters in hippocampal nerve terminals
callnumber	QH301-705.5
title_auth	Interactions between Glycine and Glutamate through Activation of Their Transporters in Hippocampal Nerve Terminals
abstract	Evidence supports the pathophysiological relevance of crosstalk between the neurotransmitters Glycine and Glutamate and their close interactions; some reports even support the possibility of Glycine–Glutamate cotransmission in central nervous system (CNS) areas, including the hippocampus. Functional studies with isolated nerve terminals (synaptosomes) permit us to study transporter-mediated interactions between neurotransmitters that lead to the regulation of transmitter release. Our main aims here were: (i) to investigate release-regulating, transporter-mediated interactions between Glycine and Glutamate in hippocampal nerve terminals and (ii) to determine the coexistence of transporters for Glycine and Glutamate in these terminals. Purified synaptosomes, analyzed at the ultrastructural level via electron microscopy, were used as the experimental model. Mouse hippocampal synaptosomes were prelabeled with [<sup<3</sup<H]D-Aspartate or [<sup<3</sup<H]Glycine; the release of radiolabeled tracers was monitored with the superfusion technique. The main findings were that (i) exogenous Glycine stimulated [<sup<3</sup<H]D-Aspartate release, partly by activation of GlyT1 and in part, unusually, through GlyT2 transporters and that (ii) D-Aspartate stimulated [<sup<3</sup<H]glycine release by a process that was sensitive to Glutamate transporter blockers. Based on the features of the experimental model used, it is suggested that functional transporters for Glutamate and Glycine coexist in a small subset of hippocampal nerve terminals, a condition that may also be compatible with cotransmission; glycinergic and glutamatergic transporters exhibit different functions and mediate interactions between the neurotransmitters. It is hoped that increased information on Glutamate–Glycine interactions in different areas, including the hippocampus, will contribute to a better knowledge of drugs acting at “glycinergic” targets, currently under study in relation with different CNS pathologies.
abstractGer	Evidence supports the pathophysiological relevance of crosstalk between the neurotransmitters Glycine and Glutamate and their close interactions; some reports even support the possibility of Glycine–Glutamate cotransmission in central nervous system (CNS) areas, including the hippocampus. Functional studies with isolated nerve terminals (synaptosomes) permit us to study transporter-mediated interactions between neurotransmitters that lead to the regulation of transmitter release. Our main aims here were: (i) to investigate release-regulating, transporter-mediated interactions between Glycine and Glutamate in hippocampal nerve terminals and (ii) to determine the coexistence of transporters for Glycine and Glutamate in these terminals. Purified synaptosomes, analyzed at the ultrastructural level via electron microscopy, were used as the experimental model. Mouse hippocampal synaptosomes were prelabeled with [<sup<3</sup<H]D-Aspartate or [<sup<3</sup<H]Glycine; the release of radiolabeled tracers was monitored with the superfusion technique. The main findings were that (i) exogenous Glycine stimulated [<sup<3</sup<H]D-Aspartate release, partly by activation of GlyT1 and in part, unusually, through GlyT2 transporters and that (ii) D-Aspartate stimulated [<sup<3</sup<H]glycine release by a process that was sensitive to Glutamate transporter blockers. Based on the features of the experimental model used, it is suggested that functional transporters for Glutamate and Glycine coexist in a small subset of hippocampal nerve terminals, a condition that may also be compatible with cotransmission; glycinergic and glutamatergic transporters exhibit different functions and mediate interactions between the neurotransmitters. It is hoped that increased information on Glutamate–Glycine interactions in different areas, including the hippocampus, will contribute to a better knowledge of drugs acting at “glycinergic” targets, currently under study in relation with different CNS pathologies.
abstract_unstemmed	Evidence supports the pathophysiological relevance of crosstalk between the neurotransmitters Glycine and Glutamate and their close interactions; some reports even support the possibility of Glycine–Glutamate cotransmission in central nervous system (CNS) areas, including the hippocampus. Functional studies with isolated nerve terminals (synaptosomes) permit us to study transporter-mediated interactions between neurotransmitters that lead to the regulation of transmitter release. Our main aims here were: (i) to investigate release-regulating, transporter-mediated interactions between Glycine and Glutamate in hippocampal nerve terminals and (ii) to determine the coexistence of transporters for Glycine and Glutamate in these terminals. Purified synaptosomes, analyzed at the ultrastructural level via electron microscopy, were used as the experimental model. Mouse hippocampal synaptosomes were prelabeled with [<sup<3</sup<H]D-Aspartate or [<sup<3</sup<H]Glycine; the release of radiolabeled tracers was monitored with the superfusion technique. The main findings were that (i) exogenous Glycine stimulated [<sup<3</sup<H]D-Aspartate release, partly by activation of GlyT1 and in part, unusually, through GlyT2 transporters and that (ii) D-Aspartate stimulated [<sup<3</sup<H]glycine release by a process that was sensitive to Glutamate transporter blockers. Based on the features of the experimental model used, it is suggested that functional transporters for Glutamate and Glycine coexist in a small subset of hippocampal nerve terminals, a condition that may also be compatible with cotransmission; glycinergic and glutamatergic transporters exhibit different functions and mediate interactions between the neurotransmitters. It is hoped that increased information on Glutamate–Glycine interactions in different areas, including the hippocampus, will contribute to a better knowledge of drugs acting at “glycinergic” targets, currently under study in relation with different CNS pathologies.
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title_short	Interactions between Glycine and Glutamate through Activation of Their Transporters in Hippocampal Nerve Terminals
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author2	Maria Cristina Gagliani Luca Raiteri
author2Str	Maria Cristina Gagliani Luca Raiteri
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up_date	2024-07-03T19:55:17.441Z
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