Homocysteine and A2A-D2 Receptor-Receptor Interaction at Striatal Astrocyte Processes

C Cervetto, A Venturini, D Guidolin, G Maura, M Passalacqua, C Tacchetti, P Cortelli, S Genedani, S Candiani, P Ramoino, S Pelassa, M Marcoli, LF Agnati

Research output: Contribution to journalArticle

Abstract

The interaction between adenosine A2A and dopamine D2 receptors in striatal neurons is a well-established phenomenon and has opened up new perspectives on the molecular mechanisms involved in Parkinson’s disease. However, it has barely been investigated in astrocytes. Here, we show by immunofluorescence that both A2A and D2 receptors are expressed in adult rat striatal astrocytes in situ, and investigate on presence, function, and interactions of the receptors in the astrocyte processes—acutely prepared from the adult rat striatum—and on the effects of homocysteine on the A2A-D2 receptor-receptor interaction. We found that A2A and D2 receptors were co-expressed on vesicular glutamate transporter-1-positive astrocyte processes, and confirmed that A2A-D2 receptor-receptor interaction controlled glutamate release—assessed by measuring the [3H]D-aspartate release—from the processes. The complexity of A2A-D2 receptor-receptor interaction is suggested by the effect of intracellular homocysteine, which reduced D2-mediated inhibition of glutamate release (homocysteine allosteric action on D2), without interfering with the A2A-mediated antagonism of the D2 effect (maintained A2A-D2 interaction). Our findings indicate the crucial integrative role of A2A-D2 molecular circuits at the plasma membrane of striatal astrocyte processes. The fact that homocysteine reduced D2-mediated inhibition of glutamate release could provide new insights into striatal astrocyte-neuron intercellular communications. As striatal astrocytes are recognized to be involved in Parkinson’s pathophysiology, these findings may shed light on the pathogenic mechanisms of the disease and contribute to the development of new drugs for its treatment. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
Original languageEnglish
Pages (from-to)456-466
Number of pages11
JournalJournal of Molecular Neuroscience
Volume65
Issue number4
DOIs
Publication statusPublished - 2018

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Corpus Striatum
Homocysteine
Astrocytes
Glutamic Acid
Vesicular Glutamate Transport Protein 1
D-Aspartic Acid
Neurons
Dopamine D2 Receptors
Adenosine
Fluorescent Antibody Technique
Parkinson Disease
Cell Membrane
Pharmaceutical Preparations

Cite this

Homocysteine and A2A-D2 Receptor-Receptor Interaction at Striatal Astrocyte Processes. / Cervetto, C; Venturini, A; Guidolin, D; Maura, G; Passalacqua, M; Tacchetti, C; Cortelli, P; Genedani, S; Candiani, S; Ramoino, P; Pelassa, S; Marcoli, M; Agnati, LF.

In: Journal of Molecular Neuroscience, Vol. 65, No. 4, 2018, p. 456-466.

Research output: Contribution to journalArticle

Cervetto, C, Venturini, A, Guidolin, D, Maura, G, Passalacqua, M, Tacchetti, C, Cortelli, P, Genedani, S, Candiani, S, Ramoino, P, Pelassa, S, Marcoli, M & Agnati, LF 2018, 'Homocysteine and A2A-D2 Receptor-Receptor Interaction at Striatal Astrocyte Processes', Journal of Molecular Neuroscience, vol. 65, no. 4, pp. 456-466. https://doi.org/10.1007/s12031-018-1120-4
Cervetto, C ; Venturini, A ; Guidolin, D ; Maura, G ; Passalacqua, M ; Tacchetti, C ; Cortelli, P ; Genedani, S ; Candiani, S ; Ramoino, P ; Pelassa, S ; Marcoli, M ; Agnati, LF. / Homocysteine and A2A-D2 Receptor-Receptor Interaction at Striatal Astrocyte Processes. In: Journal of Molecular Neuroscience. 2018 ; Vol. 65, No. 4. pp. 456-466.
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AU - Passalacqua, M

AU - Tacchetti, C

AU - Cortelli, P

AU - Genedani, S

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AB - The interaction between adenosine A2A and dopamine D2 receptors in striatal neurons is a well-established phenomenon and has opened up new perspectives on the molecular mechanisms involved in Parkinson’s disease. However, it has barely been investigated in astrocytes. Here, we show by immunofluorescence that both A2A and D2 receptors are expressed in adult rat striatal astrocytes in situ, and investigate on presence, function, and interactions of the receptors in the astrocyte processes—acutely prepared from the adult rat striatum—and on the effects of homocysteine on the A2A-D2 receptor-receptor interaction. We found that A2A and D2 receptors were co-expressed on vesicular glutamate transporter-1-positive astrocyte processes, and confirmed that A2A-D2 receptor-receptor interaction controlled glutamate release—assessed by measuring the [3H]D-aspartate release—from the processes. The complexity of A2A-D2 receptor-receptor interaction is suggested by the effect of intracellular homocysteine, which reduced D2-mediated inhibition of glutamate release (homocysteine allosteric action on D2), without interfering with the A2A-mediated antagonism of the D2 effect (maintained A2A-D2 interaction). Our findings indicate the crucial integrative role of A2A-D2 molecular circuits at the plasma membrane of striatal astrocyte processes. The fact that homocysteine reduced D2-mediated inhibition of glutamate release could provide new insights into striatal astrocyte-neuron intercellular communications. As striatal astrocytes are recognized to be involved in Parkinson’s pathophysiology, these findings may shed light on the pathogenic mechanisms of the disease and contribute to the development of new drugs for its treatment. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

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