Dopamine D2 receptors are involved in the regulation of Fyn and metabotropic glutamate receptor 5 phosphorylation in the rat striatum in vivo

Journal of Neuroscience Research
Limin Mao, John Q Wang

Abstract

Fyn, a major Src family kinase (SFK) member that is densely expressed in striatal neurons, is actively involved in the regulation of cellular and synaptic activities in local neurons. This SFK member is likely regulated by dopamine signaling through a receptor mechanism involving dopamine D2 receptors (D2Rs). This study characterizes the D2R-dependent regulation of Fyn in the rat striatum in vivo. Moreover, we explore whether D2Rs regulate metabotropic glutamate receptor 5 (mGluR5) in its tyrosine phosphorylation and whether the D2R-SFK pathway modulates trafficking of mGluR5. We found that blockade of D2Rs by systemic administration of a D2R antagonist, eticlopride, substantially increased SFK phosphorylation in the striatum. This increase was a transient and reversible event. The eticlopride-induced SFK phosphorylation occurred predominantly in immunopurified Fyn but not in another SFK member, Src. Eticlopride also elevated tyrosine phosphorylation of mGluR5. In parallel, eticlopride enhanced synaptic delivery of active Fyn and mGluR5. Pretreatment with an SFK inhibitor blocked the eticlopride-induced tyrosine phosphorylation and synaptic trafficking of mGluR5. These results indicate that D2Rs inhibit SFK (mainly Fyn) phospho...Continue Reading

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Citations

Feb 9, 2017·Journal of Molecular Neuroscience : MN·Li-Min Mao, John Q Wang
Aug 26, 2017·Molecular Neurobiology·Sara Sanz-BlascoJuan E Ferrario
May 12, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Giulio PoliTiziano Tuccinardi
Mar 14, 2018·Journal of Molecular Neuroscience : MN·Li-Min MaoJohn Q Wang
Nov 12, 2020·Molecular Neurobiology·Efthalia AngelopoulouChristina Piperi
Sep 6, 2018·Journal of Medicinal Chemistry·Mingcheng QianSerge Van Calenbergh

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