Differential expression of AMPA receptor subunits in substance P receptor-containing neurons of the caudate-putamen of rats

Neurosci Res. 2004 Jul;49(3):281-8. doi: 10.1016/j.neures.2004.03.003.


Previous evidence has suggested that glutamate-driving neurotransmission and glutamate-excitotoxicity are modulated by substance P in the basal ganglia, but the assembly of glutamate receptors mediating this process remains to be delineated. By using a double immunofluorescence, cellular expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor subunits (GluR1-4) in substance P receptor (SPR)-containing neurons was examined in the striatum of rats. It revealed that distribution of SPR-immunoreactive neurons completely overlapped with that of GluR1, 2, 3 or 4-immunoreactive neurons in the caudate-putamen. Neurons showing both SPR and AMPA receptor subunits (except of GluR3)-immunoreactivity were observed: all (100%) of SPR-positive neurons displayed GluR1-, GluR2- or GluR4-immunoreactivity, and the double-labeled neurons constituted about 33, 3 or 29% of total GluR-positive ones. In contrast, the neurons exhibiting both SPR- and GluR3-immunoreactivity were not detected, though numerous GluR3-positive neurons were still distributed in the caudate-putamen regions. Co-localization of SPR and distinct AMPA receptor subunits in the striatal neurons has provided a basis for functional modulation of neuronal APMA receptors by substance P in the caudate-putamen of rodents. Taken together with previous observations, this study has also suggested that, through interaction with AMPA receptors composed of subunits 1, 2 and 4, substance P or neurokinin peptides may play important roles in regulating neuronal properties and protecting neurons from excitotoxicity in the basal ganglia of mammals.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caudate Nucleus / cytology
  • Gene Expression Regulation / physiology
  • Immunohistochemistry / methods
  • Male
  • Neostriatum / cytology*
  • Neostriatum / metabolism
  • Neurons / metabolism*
  • Protein Subunits / metabolism
  • Putamen / cytology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism*
  • Receptors, Neurokinin-1 / metabolism*


  • Protein Subunits
  • Receptors, AMPA
  • Receptors, Neurokinin-1