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Upregulation of Src Family Tyrosine Kinases in the Rat Striatum by Adenosine A2A Receptors

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Abstract

Adenosine A2A receptors are Golf-coupled receptors and are predominantly expressed in the striatum of mammalian brains. As a mostly postsynaptic receptor, A2A receptors are implicated in the regulation of a variety of intracellular signaling pathways in striatopallidal output neurons and are linked to the pathogenesis of various neuropsychiatric and neurological disorders. This study investigated the possible role of A2A receptors in the modulation of the Src family kinase (SFK) in the adult rat striatum. In acutely prepared striatal slices, adding the A2A receptor agonist PSB-0777 induced a significant increase in phosphorylation of SFKs at a conserved autophosphorylation site (Y416) in the caudate putamen (CPu). This increase was also seen in the nucleus accumbens (NAc). Another A2A agonist CGS-21680 showed the similar ability to elevate SFK Y416 phosphorylation in the striatum. Treatment with the A2A receptor antagonist KW-6002 blocked the effect of PSB-0777 on SFK Y416 phosphorylation. In addition, PSB-0777 enhanced kinase activity of two key SFK members (Src and Fyn) immunoprecipitated from the striatum. These data demonstrate a positive linkage from A2A receptors to the SFK signaling pathway in striatal neurons. Activation of A2A receptors leads to the upregulation of phosphorylation of SFKs (Src and Fyn) at an activation-associated autophosphorylation site and kinase activity of these SFK members.

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Availability of Data and Materials

The data sets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors want to thank Dr. Daozhong Jin and Dr. Hunter J. Faris for their technical assistance.

Funding

This work was supported by the NIH grant R01MH061469 (J.Q.W.).

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Authors and Affiliations

  1. Department of Biomedical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA

    Li-Min Mao, Shannon Demehri & John Q. Wang

  2. Department of Anesthesiology, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA

    John Q. Wang

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  1. Li-Min Mao
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Contributions

LMM and JQW designed the study. LMM and SD performed the experiments and collected the data. LMM, SD, and JQW analyzed data. LMM and JQW drafted the manuscript. All authors reviewed and edited the manuscript and approved the final manuscript.

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Correspondence to John Q. Wang.

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The animal protocol was approved by the Institutional Animal Care and Use Committee (protocol no.: 1006).

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Mao, LM., Demehri, S. & Wang, J.Q. Upregulation of Src Family Tyrosine Kinases in the Rat Striatum by Adenosine A2A Receptors. J Mol Neurosci 72, 802–811 (2022). https://doi.org/10.1007/s12031-021-01961-0

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