Roles of adenosine A1 receptors in the regulation of SFK activity in the rat forebrain
Abstract Adenosine A1 receptors are widely expressed in the mammalian brain. Through interacting with Gαi/o‐coupled A1 receptors, the neuromodulator adenosine modulates a variety of cellular and synaptic activities. To determine the linkage from A1 receptors to a key intracellular signaling pathway,...
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| Format: | Article |
| Language: | English |
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Wiley
2021-08-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.2254 |
| _version_ | 1797754630645481472 |
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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 Adenosine A1 receptors are widely expressed in the mammalian brain. Through interacting with Gαi/o‐coupled A1 receptors, the neuromodulator adenosine modulates a variety of cellular and synaptic activities. To determine the linkage from A1 receptors to a key intracellular signaling pathway, we investigated the impact of blocking A1 receptors on a subfamily of nonreceptor tyrosine kinases, that is, the Src family kinase (SFK), in different rat brain regions in vivo. We found that pharmacological blockade of A1 receptors by a single systemic injection of the A1 selective antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX) induced an increase in autophosphorylation of SFKs at a consensus activation site, tyrosine 416 (Y416), in the two subdivisions of the striatum, the caudate putamen and nucleus accumbens. DPCPX also increased SFK Y416 phosphorylation in the medial prefrontal cortex (mPFC) but not the hippocampus. The DPCPX‐induced Y416 phosphorylation was time dependent and reversible. In immunopurified Fyn and Src proteins from the striatum, DPCPX elevated SFK Y416 phosphorylation and tyrosine kinase activity in Fyn but not in Src proteins. In the mPFC, DPCPX enhanced Y416 phosphorylation and tyrosine kinase activity in both Fyn and Src immunoprecipitates. DPCPX had no effect on expression of total Fyn and Src proteins in the striatum, mPFC, and hippocampus. These results demonstrate a tonic inhibitory linkage from A1 receptors to SFKs in the striatum and mPFC. Blocking this inhibitory tone could significantly enhance constitutive SFK Y416 phosphorylation in the rat brain in a region‐ and time‐dependent manner. |
| first_indexed | 2024-03-12T17:36:16Z |
| format | Article |
| id | doaj.art-0937414a78f94f3aa5eda59cb8980a9f |
| institution | Directory Open Access Journal |
| issn | 2162-3279 |
| language | English |
| last_indexed | 2024-03-12T17:36:16Z |
| publishDate | 2021-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj.art-0937414a78f94f3aa5eda59cb8980a9f2023-08-04T10:56:25ZengWileyBrain and Behavior2162-32792021-08-01118n/an/a10.1002/brb3.2254Roles of adenosine A1 receptors in the regulation of SFK activity in the rat forebrainLi‐Min Mao0John Q. Wang1Department of Biomedical Sciences School of Medicine University of Missouri‐Kansas City Kansas City Missouri USADepartment of Biomedical Sciences School of Medicine University of Missouri‐Kansas City Kansas City Missouri USAAbstract Adenosine A1 receptors are widely expressed in the mammalian brain. Through interacting with Gαi/o‐coupled A1 receptors, the neuromodulator adenosine modulates a variety of cellular and synaptic activities. To determine the linkage from A1 receptors to a key intracellular signaling pathway, we investigated the impact of blocking A1 receptors on a subfamily of nonreceptor tyrosine kinases, that is, the Src family kinase (SFK), in different rat brain regions in vivo. We found that pharmacological blockade of A1 receptors by a single systemic injection of the A1 selective antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX) induced an increase in autophosphorylation of SFKs at a consensus activation site, tyrosine 416 (Y416), in the two subdivisions of the striatum, the caudate putamen and nucleus accumbens. DPCPX also increased SFK Y416 phosphorylation in the medial prefrontal cortex (mPFC) but not the hippocampus. The DPCPX‐induced Y416 phosphorylation was time dependent and reversible. In immunopurified Fyn and Src proteins from the striatum, DPCPX elevated SFK Y416 phosphorylation and tyrosine kinase activity in Fyn but not in Src proteins. In the mPFC, DPCPX enhanced Y416 phosphorylation and tyrosine kinase activity in both Fyn and Src immunoprecipitates. DPCPX had no effect on expression of total Fyn and Src proteins in the striatum, mPFC, and hippocampus. These results demonstrate a tonic inhibitory linkage from A1 receptors to SFKs in the striatum and mPFC. Blocking this inhibitory tone could significantly enhance constitutive SFK Y416 phosphorylation in the rat brain in a region‐ and time‐dependent manner.https://doi.org/10.1002/brb3.2254RRID:SCR_002798caudate putamenDPCPXFynnucleus accumbensprefrontal cortex |
| spellingShingle | Li‐Min Mao John Q. Wang Roles of adenosine A1 receptors in the regulation of SFK activity in the rat forebrain Brain and Behavior RRID:SCR_002798 caudate putamen DPCPX Fyn nucleus accumbens prefrontal cortex |
| title | Roles of adenosine A1 receptors in the regulation of SFK activity in the rat forebrain |
| title_full | Roles of adenosine A1 receptors in the regulation of SFK activity in the rat forebrain |
| title_fullStr | Roles of adenosine A1 receptors in the regulation of SFK activity in the rat forebrain |
| title_full_unstemmed | Roles of adenosine A1 receptors in the regulation of SFK activity in the rat forebrain |
| title_short | Roles of adenosine A1 receptors in the regulation of SFK activity in the rat forebrain |
| title_sort | roles of adenosine a1 receptors in the regulation of sfk activity in the rat forebrain |
| topic | RRID:SCR_002798 caudate putamen DPCPX Fyn nucleus accumbens prefrontal cortex |
| url | https://doi.org/10.1002/brb3.2254 |
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