Activation of phosphatidylinositol-linked D1-like receptors increases spontaneous glutamate release in rat somatosensory cortical neurons in vitro

Hong Yuan Chu, Zhi Yang, Bin Zhao, Guo Zhang Jin, Guo Yuan Hu, Xuechu Zhen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Central dopaminergic system exerts profound modulation on spontaneous glutamate release in various brain regions mainly through D1 receptor/cAMP/PKA pathway. It remains unclear whether the phosphatidylinositol (PI)-linked D1-like receptors are also involved in such modulatory actions. The identification of substituted phenylbenzazepine SKF83959 as the selective agonist for the atypical D1-like receptors has given impetus to study their influence on the spontaneous glutamate release in the brain. In the present study the effects of SKF83959 on the spontaneous excitatory postsynaptic currents (sEPSCs) were investigated through whole-cell recording from layer V-VI pyramidal neurons in rat somatosensory cortical slices. Perfusion with SKF83959 (10-100 μM) considerably increased the frequency of sEPSCs, while had no significant effect on the amplitude of sEPSCs. The increase of sEPSC frequency by SKF83959 was blocked by SCH23390, a D1-like receptor antagonist, but not by the antagonists for D2 receptor, α1-adrenoceptor and 5-HT2A/2C receptor. U-73122 (PLCβ inhibitor), 2-APB (IP3 receptor antagonist), chelerythrine chloride (PKC inhibitor) and capsazepine (TRPV1 antagonist) could block the effects of SKF83959, whereas H-89 (PKA inhibitor) and forskolin (adenylyl cyclase activator) had no effect. Taken together, sensitization of TRPV1 channels by PKC after activation of D1 receptor/PLCβ signaling pathway mediated SKF83959-induced increase in the sEPSC frequency. To our knowledge, this is the first pharmacological evidence that PI-linked D1-like dopamine receptors do exist in presynaptic terminals of cortical neurons and play an important role in controlling the spontaneous glutamate release.

Original languageEnglish (US)
Pages (from-to)20-27
Number of pages8
JournalBrain research
Volume1343
DOIs
StatePublished - Jul 9 2010

Keywords

  • Dopamine receptor
  • Glutamate release
  • Protein kinase C
  • SKF83959
  • Spontaneous excitatory postsynaptic current
  • Transient receptor potential vanilloid 1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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