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.