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Published on: August 16, 2018
AMPA (amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptors in human brain tissues
D G Sawutz1, D S Krafte, J J Oleynek
1Department of Biochemistry, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, PA 19426, USA.
Journal of Receptor and Signal Transduction Research
|July 1, 1995
Summary
A new assay using [3H]-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) allows for specific binding to AMPA receptors in human brain tissue. This method aids in screening for neuroprotective drugs targeting neurodegenerative diseases.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- AMPA receptors are implicated in acute and chronic neurodegenerative diseases.
- Selective antagonists for AMPA receptors are sought for therapeutic applications.
Purpose of the Study:
- To describe a novel assay for specific [3H]-AMPA binding to human brain membranes.
- To evaluate the utility of this assay for screening AMPA receptor antagonists.
Main Methods:
- Preparation of membranes from post-mortem human hippocampus and fetal brain.
- Characterization of [3H]-AMPA binding kinetics (saturation, Scatchard analysis, association/dissociation rates).
- Pharmacological profiling using various agonists and antagonists, including DNQX and CNQX.
Main Results:
- [3H]-AMPA binding to human hippocampus membranes was saturable, revealing high and low affinity sites.
- Binding affinity constants (KD) were determined to be 3.4 +/- 0.5 nM and 65 +/- 9 nM.
- Pharmacology of human brain AMPA receptors was comparable to known profiles, and functional expression was achieved in frog oocytes.
Conclusions:
- The developed [3H]-AMPA binding assay is suitable for screening selective AMPA receptor antagonists.
- Human brain tissues can be effectively used for both screening and functional analysis of potential therapeutic agents targeting AMPA receptors.
- This research provides a valuable tool for developing treatments for neurodegenerative conditions.
