beta-Amyloid related peptides exert differential effects on [3H]MK-801 binding to rat cortical membranes.
The effects of beta-amyloid protein 1-40 (beta AP 1-40), substance P (SP), and the amidated and carboxylic acid C-terminated forms of the SP homologous beta AP fragment 25-35 (beta AP 25-35-NH2 and beta AP 25-35-COOH) were studied on [3H]MK-801 binding to the rat brain NMDA receptor cation channel. All peptides gave dose-dependent enhancements of [3H]MK-801 binding stimulated by low glycine. beta AP 25-35-COOH, but not beta AP 25-35-NH2 produced an inhibition of [3H]MK-801 binding stimulated by high glycine in the presence of either low or high glutamate. Low glutamate-stimulated [3H]MK-801 binding was also inhibited by SP but not by beta AP 1-40. It is concluded that beta AP related peptides exert differential effects on the NMDA receptor complex at the glycine and possibly also the glutamate recognition sites.
Cowburn
R F
RF
Karolinska Institute, Department of Geriatric Medicine, Huddinge University Hospital, Sweden.
Messamore
E
E
Li
M L
ML
Winblad
B
B
Sundström
E
E
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000494:pharmacology*; D014316:Tritium
D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D014316:Tritium; D013373:Substance P; D016291:Dizocilpine Maleate