D1 dopamine receptor-induced cyclic AMP-dependent protein kinase phosphorylation and potentiation of striatal glutamate receptors.
Dopamine receptor activation regulates cyclic AMP levels and is critically involved in modulating neurotransmission in the striatum. Others have shown that alpha-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 microM), kainate-evoked current amplitude was enhanced in approximately 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 Ser845 of GluR1, we observed a marked increase in phosphorylated GluR1 following a 10-min exposure of striatal neurons to 1 microM 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.
Price
C J
CJ
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Kim
P
P
Raymond
L A
LA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001569:Benzodiazepines; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D014151:Anti-Anxiety Agents; D001552:Benzazepines; D001569:Benzodiazepines; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; C061950:GYKI 52466; C067113:SK&F 81297