D2‐class dopamine receptor inhibition of NMDA currents in prefrontal cortical neurons is platelet‐derived growth factor receptor‐dependent

• Published in: Journal of neurochemistry Vol. 98; no. 5; pp. 1657 - 1663
• Main Authors: Beazely, Michael A., Tong, Andrew, Wei, Wen‐Li, Van Tol, Hubert, Sidhu, Bikram, MacDonald, John F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-2006; Blackwell
• Subjects: Animals; Animals, Newborn; Benzamides - pharmacology; Biological and medical sciences; Biotinylation - methods; Blotting, Western - methods; Cell receptors; Cell structures and functions; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; dopamine; Dopamine Agonists - pharmacology; Dopamine Antagonists - pharmacology; Drug Interactions; Enzymes; Excitatory Amino Acid Agonists - pharmacology; Fundamental and applied biological sciences. Psychology; hippocampus; Hippocampus - cytology; Hormones; In Vitro Techniques; Membrane Potentials - drug effects; Membrane Potentials - physiology; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); N-Methylaspartate - pharmacology; Neural Inhibition - drug effects; Neural Inhibition - physiology; Neurons; Neurons - drug effects; Neurons - physiology; Patch-Clamp Techniques - methods; phospholipase C; Piperazines - pharmacology; Platelet-Derived Growth Factor - pharmacology; platelet‐derived growth factor; prefrontal cortex; Prefrontal Cortex - cytology; Proteins; Quinpirole - pharmacology; Raclopride - pharmacology; Rats; Rats, Wistar; Receptors, Dopamine D2 - physiology; Receptors, Platelet-Derived Growth Factor - physiology; Rodents; Vertebrates: nervous system and sense organs; Rat; prefrontal cortex; Central nervous system; platelet-derived growth factor; Esterases; Glutamate receptor; Activation; Phosphoric diester hydrolases; Encephalon; Platelet derived growth factor; G protein; Biological receptor; D4 Dopamine receptor; Tyrosine; Enzyme; Transferases; Rodentia; Catecholamine; Phospholipase C; Vertebrata; Mammalia; Neuron; D2 Dopamine receptor; Kinase; Neurotransmitter; Hydrolases; NMDA receptor; dopamine; Hippocampus
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.04064.x

NMDA receptor function is modulated by both G‐protein‐coupled receptors and receptor tyrosine kinases. In acutely isolated rat hippocampal neurons, direct activation of the platelet‐derived growth factor (PDGF) receptor or transactivation of the PDGF receptor by D4 dopamine receptors inhibits NMDA‐evoked currents in a phospholipase C (PLC)‐dependent manner. We have investigated further the ability of D2‐class dopamine receptors to modulate NMDA‐evoked currents in isolated rat prefrontal cortex (PFC). We have demonstrated that, similar to isolated hippocampal neurons, the application of PDGF‐BB or quinpirole to isolated PFC neurons induces a slow‐onset and long‐lasting inhibition of NMDA‐evoked currents. However, in contrast to hippocampal neurons, the inhibition of NMDA‐evoked currents by quinpirole in PFC neurons is dependent upon D2/3, rather than D4, dopamine receptors. In PFC slices, application of both PDGF‐BB and quinpirole induced a phosphorylation of the PDGF receptor at the PLCγ binding and activation site, Tyr1021. The PDGF receptor kinase inhibitor, tyrphostin A9, and the D2/3 dopamine receptor antagonist, raclopride, inhibited quinpirole‐induced Tyr1021 phosphorylation. These finding suggest that quinpirole treatment inhibits NMDAR signaling via PDGF receptor transactivation in both the hippocampus and the PFC, and that the effects of quinpirole in these regions are mediated by D4 and D2/3 dopamine receptors, respectively.