Upregulation of AMPA receptor GluA1 phosphorylation by blocking adenosine A1 receptors in the male rat forebrain
Abstract Objective The adenosine A1 receptor is a Gαi/o protein‐coupled receptor and inhibits upon activation cAMP formation and protein kinase A (PKA) activity. As a widely expressed receptor in the mammalian brain, A1 receptors are implicated in the modulation of a variety of neuronal and synaptic...
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| Format: | Article |
| Language: | English |
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Wiley
2020-03-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.1543 |
| _version_ | 1818977779015745536 |
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| author | Li‐Min Mao John Q. Wang |
| author_facet | Li‐Min Mao John Q. Wang |
| author_sort | Li‐Min Mao |
| collection | DOAJ |
| description | Abstract Objective The adenosine A1 receptor is a Gαi/o protein‐coupled receptor and inhibits upon activation cAMP formation and protein kinase A (PKA) activity. As a widely expressed receptor in the mammalian brain, A1 receptors are implicated in the modulation of a variety of neuronal and synaptic activities. In this study, we investigated the role of A1 receptors in the regulation of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors in the adult rat brain in vivo. Methods Adult male Wistar rats were used in this study. After a systemic injection of the A1 antagonist DPCPX, rats were sacrificed and several forebrain regions were collected for assessing changes in phosphorylation of AMPA receptors using Western blots. Results A systemic injection of the A1 antagonist DPCPX induced an increase in phosphorylation of AMPA receptor GluA1 subunits at a PKA‐dependent site, serine 845 (S845), in the two subdivisions of the striatum, the caudate putamen, and nucleus accumbens. DPCPX also increased S845 phosphorylation in the medial prefrontal cortex (mPFC) and hippocampus. The DPCPX‐stimulated S845 phosphorylation was a transient and reversible event. Blockade of Gαs/olf‐coupled dopamine D1 receptors with a D1 antagonist SCH23390 abolished the responses of S845 phosphorylation to DPCPX in the striatum, mPFC, and hippocampus. DPCPX had no significant impact on phosphorylation of GluA1 at serine 831 and on expression of total GluA1 proteins in all forebrain regions surveyed. Conclusion These data demonstrate that adenosine A1 receptors maintain an inhibitory tone on GluA1 S845 phosphorylation under normal conditions. Blocking this inhibitory tone leads to the upregulation of GluA1 S845 phosphorylation in the striatum, mPFC, and hippocampus via a D1‐dependent manner. |
| first_indexed | 2024-12-20T16:33:09Z |
| format | Article |
| id | doaj.art-15641756e3cf4844acd236767c14420c |
| institution | Directory Open Access Journal |
| issn | 2162-3279 |
| language | English |
| last_indexed | 2024-12-20T16:33:09Z |
| publishDate | 2020-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj.art-15641756e3cf4844acd236767c14420c2022-12-21T19:33:13ZengWileyBrain and Behavior2162-32792020-03-01103n/an/a10.1002/brb3.1543Upregulation of AMPA receptor GluA1 phosphorylation by blocking adenosine A1 receptors in the male rat forebrainLi‐Min Mao0John Q. Wang1Department of Biomedical Sciences School of Medicine University of Missouri‐Kansas City Kansas City MO USADepartment of Biomedical Sciences School of Medicine University of Missouri‐Kansas City Kansas City MO USAAbstract Objective The adenosine A1 receptor is a Gαi/o protein‐coupled receptor and inhibits upon activation cAMP formation and protein kinase A (PKA) activity. As a widely expressed receptor in the mammalian brain, A1 receptors are implicated in the modulation of a variety of neuronal and synaptic activities. In this study, we investigated the role of A1 receptors in the regulation of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors in the adult rat brain in vivo. Methods Adult male Wistar rats were used in this study. After a systemic injection of the A1 antagonist DPCPX, rats were sacrificed and several forebrain regions were collected for assessing changes in phosphorylation of AMPA receptors using Western blots. Results A systemic injection of the A1 antagonist DPCPX induced an increase in phosphorylation of AMPA receptor GluA1 subunits at a PKA‐dependent site, serine 845 (S845), in the two subdivisions of the striatum, the caudate putamen, and nucleus accumbens. DPCPX also increased S845 phosphorylation in the medial prefrontal cortex (mPFC) and hippocampus. The DPCPX‐stimulated S845 phosphorylation was a transient and reversible event. Blockade of Gαs/olf‐coupled dopamine D1 receptors with a D1 antagonist SCH23390 abolished the responses of S845 phosphorylation to DPCPX in the striatum, mPFC, and hippocampus. DPCPX had no significant impact on phosphorylation of GluA1 at serine 831 and on expression of total GluA1 proteins in all forebrain regions surveyed. Conclusion These data demonstrate that adenosine A1 receptors maintain an inhibitory tone on GluA1 S845 phosphorylation under normal conditions. Blocking this inhibitory tone leads to the upregulation of GluA1 S845 phosphorylation in the striatum, mPFC, and hippocampus via a D1‐dependent manner.https://doi.org/10.1002/brb3.1543caudate putamenDPCPXGluA1hippocampusnucleus accumbensphosphorylation |
| spellingShingle | Li‐Min Mao John Q. Wang Upregulation of AMPA receptor GluA1 phosphorylation by blocking adenosine A1 receptors in the male rat forebrain Brain and Behavior caudate putamen DPCPX GluA1 hippocampus nucleus accumbens phosphorylation |
| title | Upregulation of AMPA receptor GluA1 phosphorylation by blocking adenosine A1 receptors in the male rat forebrain |
| title_full | Upregulation of AMPA receptor GluA1 phosphorylation by blocking adenosine A1 receptors in the male rat forebrain |
| title_fullStr | Upregulation of AMPA receptor GluA1 phosphorylation by blocking adenosine A1 receptors in the male rat forebrain |
| title_full_unstemmed | Upregulation of AMPA receptor GluA1 phosphorylation by blocking adenosine A1 receptors in the male rat forebrain |
| title_short | Upregulation of AMPA receptor GluA1 phosphorylation by blocking adenosine A1 receptors in the male rat forebrain |
| title_sort | upregulation of ampa receptor glua1 phosphorylation by blocking adenosine a1 receptors in the male rat forebrain |
| topic | caudate putamen DPCPX GluA1 hippocampus nucleus accumbens phosphorylation |
| url | https://doi.org/10.1002/brb3.1543 |
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