β-Amyloid (25-35) or Substance P Stimulates [3H]MK-801. Binding to Rat Cortical Membranes in the Presence of Glutamate and Glycine
Article first published online: 5 OCT 2006
Journal of Neurochemistry
Volume 60, Issue 6, pages 2297–2303, June 1993
How to Cite
Calligaro, D. O., O'Malley, P. J. and Monn, J. A. (1993), β-Amyloid (25-35) or Substance P Stimulates [3H]MK-801. Binding to Rat Cortical Membranes in the Presence of Glutamate and Glycine. Journal of Neurochemistry, 60: 2297–2303. doi: 10.1111/j.1471-4159.1993.tb03517.x
- Issue published online: 5 OCT 2006
- Article first published online: 5 OCT 2006
- Received September 23, 1992; revised manuscript received No- vember 16, 1992; accepted November 24, 1992.
- Substance P;
- N-Methyl-D-aspartate receptor;
- Alzheimer's, Parkinson's, and Huntington's diseases.
Abstract: Micromolar concentrations of β-amyloid (25–35) or substance P stimulated [3H] MK-801 binding in the presence of low concentrations of glutamate (1 γM) and glycine (0.02 γM). Unlike polyamines spermine and spermidine, neither β-amyloid (25–35) nor substance P increased [3H] MK-801 binding in the presence of maximally stimulating concentrations of glutamate and glycine. 5,7-Dichloro-kynurenic acid, CGS-19755, and arcaine completely inhibited the stimulated [3H] MK-801 binding. There was an apparent decreased potency of the [3H] MK-801 binding inhibition curve for 5,7-dichlorokynurenic acid, but not CGS-19755 or arcaine, in the presence of either β-amyloid (25–35) or substance P. The compounds do not appear to act through the strychnine-insensitive glycine binding site because neither β-amyloid (25–35) nor substance P displaced [3H] glycine binding. Full-length β-amyloid (1-40), up to 10 γM, did not stimulate [3H] MK-801 binding. Concentrations >10 γM could not be tested because they formed large aggregate precipitates in the assay. The data indicate that β-amyloid (25–35) or substance P does not stimulate [3H] MK-801 binding at either the N-methyl-D-aspartate, glycine, or polyamine binding sites. Furthermore, the nonpeptide substance P receptor (NK,) antagonist, CP-96,345, did not block β-amyloid (25–35)- or substance P-stimulated [3H] MK-801 binding. Therefore, the effect is not due to an interaction between the substance P receptors and the N-methyl-D-aspartate receptor-operated ionophore. Finally, if these observations can be verified using single-channel recording techniques, they may have implications in the pattern of selective neuronal loss observed in patients with neurodegenerative processes such as Alzheimer's, Parkinson's, and Huntington's diseases.