Premium
D 2 ‐class dopamine receptor inhibition of NMDA currents in prefrontal cortical neurons is platelet‐derived growth factor receptor‐dependent
Author(s) -
Beazely Michael A.,
Tong Andrew,
Wei WenLi,
Van Tol Hubert,
Sidhu Bikram,
MacDonald John F.
Publication year - 2006
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 - 10.1111/j.1471-4159.2006.04064.x
Subject(s) - neuroscience , nmda receptor , dopamine , receptor , dopamine receptor d2 , prefrontal cortex , biology , psychology , medicine , cognition
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 D 4 dopamine receptors inhibits NMDA‐evoked currents in a phospholipase C (PLC)‐dependent manner. We have investigated further the ability of D 2 ‐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 D 2/3 , rather than D 4 , 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 D 2/3 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 D 4 and D 2/3 dopamine receptors, respectively.