Inability of β-amyloid (25–35) to bind to central nervous system neurokinin 1 receptors

β-Amyloid (1–40) has recently been shown to exhibit both neurotoxic and neurotrophic properties. The putatively active moiety is β-(25–35), which has a structural homology to the human tachykinin substance P. Substance P, which preferentially binds to neurokinin 1 (NK1) receptors in the central nervous system (CNS), has been shown to block the neurotoxic effects of β-amyloid (1–40). These data suggest that effects of β-amyloid may be mediated by an NK1 receptor-mediated process. However, in the present study, we demonstrate that β-(25–35) is unable to competitively inhibit the binding of 0.15 nM ¹²⁵I-substance P from rat CNS NK1 receptors. Therefore, the mechanisms of action of β-amyloid neurotoxic effects are probably not to be mediated through a NK1 receptor-mediated process. © 1992 Wiley-Liss, Inc.