PMID:26277342

Citation	Mao, LM and Wang, JQ (2015) Dopaminergic and cholinergic regulation of Fyn tyrosine kinase phosphorylation in the rat striatum in vivo. Neuropharmacology 99:491-9
Abstract	Src and Fyn are two Src family kinase (SFK) members that are expressed in mammalian brains and play important roles in the regulation of a variety of neuronal and synaptic substrates. Here we investigated the responsiveness of these SFKs to changing dopamine receptor signals in dopamine responsive regions of adult rat brains in vivo. Pharmacological activation of dopamine D1 receptors (D1Rs) by a systemic injection of the selective agonist SKF81297 increased phosphorylation of SFKs at a conserved and activation-associated autophosphorylation site (Y416) in the striatum, indicating activation of SFKs following SKF81297 injection. The dopamine D2 receptor (D2R) agonist quinpirole had no effect. Blockade of D1Rs with an antagonist SCH23390 did not alter striatal Y416 phosphorylation, while the D2R antagonist eticlopride elevated it. Between Src and Fyn, SKF81297 seemed to preferentially facilitate Fyn phosphorylation. Activation of muscarinic acetylcholine M4 receptors (M4Rs) with a positive allosteric modulator VU0152100 suppressed SFK Y416 responses to SKF81297. Additionally, SKF81297 induced a correlated increase in phosphorylation of N-methyl-D-aspartate (NMDA) receptor GluN2B subunits at a Fyn site (Y1472), which was attenuated by VU0152100. SKF81297 also enhanced synaptic recruitments of active Fyn and GluN1/GluN2B-containing NMDA receptors. These data demonstrate that D1Rs regulate Fyn and downstream NMDA receptors in striatal neurons in vivo. Acetylcholine through activating M4Rs inhibits Fyn and NMDA receptors in their sensitivity to D1R signaling.
Links	PubMed PMC4655164 Online version:10.1016/j.neuropharm.2015.08.017
Keywords	Acetylcholine/metabolism; Animals; Corpus Striatum/drug effects; Corpus Striatum/metabolism; Dopamine/metabolism; Male; Neurons/drug effects; Neurons/metabolism; Neurotransmitter Agents/pharmacology; Phosphorylation/drug effects; Proto-Oncogene Proteins c-fyn/metabolism; Rats, Wistar; Receptor, Muscarinic M4/metabolism; Receptors, Dopamine D1/agonists; Receptors, Dopamine D1/antagonists & inhibitors; Receptors, Dopamine D1/metabolism; Receptors, Dopamine D2/agonists; Receptors, Dopamine D2/metabolism; Receptors, N-Methyl-D-Aspartate/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:DRD1	involved_in	GO:0001934: positive regulation of protein phosphorylation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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