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 Al{sup 3+} may have on G-protein mediate signal transduction, the effects of Al{sup 3+} on the signal-coupling G-protein from retinal rod outer segments (G{sub t} or transducin) have been investigated as a model for the effects of Al{sup 3+} on signal transduction by G-proteins in general. In this investigation, we have studied the effects of Al{sup 3+} on the isolated, light-dependent rhodopsin catalyzed GTP-GDP exchange on G{sub t}; the light-dependent GTPase activity of G{sub t}; 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 ({sup 3}H)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 Ca{sup 2+}, Zn{sup 2+}, Mg{sup 2+}, and Li{sup +} on the specific binding of ({sup 3}H)MK-801 to the NMDA receptor-channel complex under depolarized conditions.
- Research Organization:
- Virginia Univ., Charlottesville, VA (USA)
- OSTI ID:
- 6408155
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALUMINIUM
TOXICITY
PHOSPHOHYDROLASES
ENZYME ACTIVITY
PROTEINS
BIOCHEMICAL REACTION KINETICS
ASPARTIC ACID
CALCIUM COMPOUNDS
LEARNING
LITHIUM COMPOUNDS
MAGNESIUM COMPOUNDS
NERVOUS SYSTEM DISEASES
NUCLEOTIDES
RADIOASSAY
RETINA
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ZINC COMPOUNDS
ACID ANHYDRASES
ALKALI METAL COMPOUNDS
ALKALINE EARTH METAL COMPOUNDS
AMINO ACIDS
BODY
BODY AREAS
CARBOXYLIC ACIDS
DISEASES
ELEMENTS
ENZYMES
EYES
FACE
HEAD
HYDROGEN COMPOUNDS
HYDROLASES
ISOTOPE APPLICATIONS
KINETICS
METALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
REACTION KINETICS
SENSE ORGANS
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