On the mechanism of aluminum ion-induced neurotoxicity: The effects of aluminum species on G-protein-mediated processes and on drug interactions with the N-methyl-D-aspartate modulated ionophore

To establish what effects Al3+ may have on G-protein mediate signal transduction, the effects of Al3+ on the signal-coupling G-protein from retinal rod outer segments (Gt or transducin) have been investigated as a model for the effects of Al3+ on signal transduction by G-proteins in general. In this investigation, we have studied the effects of Al3+ on the isolated, light-dependent rhodopsin catalyzed GTP-GDP exchange on Gt; the light-dependent GTPase activity of Gt; the light-independent cGMP hydrolysis by PDE; and the light activated, rhodopsin catalyzed, cGMP hydrolysis by PDE in vitro. To determine the effects of two defined species of aluminum on N-methyl-D-aspartic acid (NMDA) receptor-channel modulation we utilized a specific radioligand binding assay. This allowed us to compare the effects of aluminum to other metal ions on specific [3H]MK-801 binding to the NMDA receptor-channel complex. This complex is involved in long-term potentiation, which is currently being investigated as the mechanism by which learning and memory occur and has been implicated in the pathology of Alzheimer's disease. We have investigated the effects of two different species of aluminum, as well as Ca2+, Zn2+, Mg2+, and Li+ on the specific binding of [3H]MK-801 to the NMDA receptor-channel complex under depolarized conditions