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D1 Dopamine Receptor‐Induced Cyclic AMP‐Dependent Protein Kinase Phosphorylation and Potentiation of Striatal Glutamate Receptors
Author(s) -
Price Christopher J.,
Kim Peter,
Raymond Lynn A.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0732441.x
Subject(s) - ampa receptor , dopamine receptor d1 , long term potentiation , agonist , sch 23390 , chemistry , dopamine , dopamine receptor , glutamate receptor , protein kinase a , neurotransmission , receptor , biology , medicine , endocrinology , phosphorylation , biochemistry
: Dopamine receptor activation regulates cyclic AMP levels and is critically involved in modulating neurotransmission in the striatum. Others have shown that α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA)‐type glutamate receptor‐mediated current is potentiated by cyclic AMP‐dependent protein kinase (PKA) activation. We made whole‐cell patch clamp recordings from cultured striatal neurons and tested whether D1‐type dopamine receptor activation affected AMPA receptor‐mediated currents. After a 5‐min exposure to the D1 agonist SKF 81297 (1 μ M ), kainate‐evoked current amplitude was enhanced in ~75% of cells to 121 ± 2.5% of that recorded prior to addition of drug. This response was inhibited by the D1 antagonist SCH 23390 and mimicked by activators of PKA. Moreover, by western blot analysis using an antibody specific for the phosphorylated PKA site Ser 845 of GluR1, we observed a marked increase in phosphorylated GluR1 following a 10‐min exposure of striatal neurons to 1 μ M SKF 81297. Our data demonstrate that activation of D1‐type dopamine receptors on striatal neurons promotes phosphorylation of AMPA receptors by PKA as well as potentiation of current amplitude. These results elucidate one mechanism by which dopamine can modulate neurotransmission in the striatum.