Heterodimer of A2A and Oxytocin Receptors Regulating Glutamate Release in Adult Striatal Astrocytes.
astrocyte processes
glutamate
heterodimers
molecular modeling
neuroglia
rat
striatum
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
19 Feb 2022
19 Feb 2022
Historique:
received:
19
01
2022
revised:
16
02
2022
accepted:
18
02
2022
entrez:
26
2
2022
pubmed:
27
2
2022
medline:
23
3
2022
Statut:
epublish
Résumé
Roles of astrocytes in the modulatory effects of oxytocin (OT) in central nervous system are increasingly considered. Nevertheless, OT effects on gliotransmitter release have been neglected. In purified astrocyte processes from adult rat striatum, we assessed OT receptor (OTR) and adenosine A2A receptor expression by confocal analysis. The effects of receptors activation on glutamate release from the processes were evaluated; A2A-OTR heteromerization was assessed by co-immunoprecipitation and PLA. Structure of the possible heterodimer of A2A and OT receptors was estimated by a bioinformatic approach. Both A2A and OT receptors were expressed on the same astrocyte processes. Evidence for A2A-OTR receptor-receptor interaction was obtained by measuring the release of glutamate: OT inhibited the evoked glutamate release, while activation of A2A receptors, per se ineffective, abolished the OT effect. Biochemical and biophysical evidence for A2A-OTR heterodimers on striatal astrocytes was also obtained. The residues in the transmembrane domains 4 and 5 of both receptors are predicted to be mainly involved in the heteromerization. When considering effects of OT in striatum, modulation of glutamate release from the astrocyte processes and of glutamatergic synapse functioning, and the interaction with A2A receptors on the astrocyte processes should be taken into consideration.
Sections du résumé
BACKGROUND
BACKGROUND
Roles of astrocytes in the modulatory effects of oxytocin (OT) in central nervous system are increasingly considered. Nevertheless, OT effects on gliotransmitter release have been neglected.
METHODS
METHODS
In purified astrocyte processes from adult rat striatum, we assessed OT receptor (OTR) and adenosine A2A receptor expression by confocal analysis. The effects of receptors activation on glutamate release from the processes were evaluated; A2A-OTR heteromerization was assessed by co-immunoprecipitation and PLA. Structure of the possible heterodimer of A2A and OT receptors was estimated by a bioinformatic approach.
RESULTS
RESULTS
Both A2A and OT receptors were expressed on the same astrocyte processes. Evidence for A2A-OTR receptor-receptor interaction was obtained by measuring the release of glutamate: OT inhibited the evoked glutamate release, while activation of A2A receptors, per se ineffective, abolished the OT effect. Biochemical and biophysical evidence for A2A-OTR heterodimers on striatal astrocytes was also obtained. The residues in the transmembrane domains 4 and 5 of both receptors are predicted to be mainly involved in the heteromerization.
CONCLUSIONS
CONCLUSIONS
When considering effects of OT in striatum, modulation of glutamate release from the astrocyte processes and of glutamatergic synapse functioning, and the interaction with A2A receptors on the astrocyte processes should be taken into consideration.
Identifiants
pubmed: 35216441
pii: ijms23042326
doi: 10.3390/ijms23042326
pmc: PMC8879615
pii:
doi:
Substances chimiques
Receptor, Adenosine A2A
0
Receptors, Oxytocin
0
Glutamic Acid
3KX376GY7L
Oxytocin
50-56-6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : FFABR (Fondo di finanziamento per le attività base di ricerca; MIUR-Italy)
ID : FFABR- to C.C. and M.M.
Organisme : Ph.D School of the Department of Experimental Medicine (University of Genova)
ID : contribution 2021 to S.A.
Organisme : MUR
ID : DIFILAB, Grant/Award Number: RBAP11ETKA-005
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