This work is directed toward the identification, purification and characterization of gamma-aminobutyric acid (GABA) and benzodiazepine receptors in mammalian brain, using a monoclonal antibody approach. Receptors for these ligands will be solubilized from rat brain and used as antigens for the preparation of monoclonal antibodies. The antibodies to rat brain GABA and benzodiazepine receptors will be used as specific probes for receptor identification, purification, distribution and turnover. These studies are aimed toward an understanding of the molecular basis of brain GABA and benzodiazepine receptor function, with an emphasis on the subunit structure of the receptors and its relationship to ligand binding, the cellular and intracellular disposition of the receptors and the relationship of GABA receptors to benzodiazepine receptors in this regard, and the dynamics of receptor synthesis and degradation. These studies should be relevant to an understanding of the biological effects of the benzodiazepines and the role of GABA and benzodiazepine receptors in mental health and disease, and also in the development of new and specific therapeutic compounds acting on specific types of GABA and benzodiazepine receptors. The scientific disciplines involved in these studies are neurobiology, neurochemistry, neuroimmunology, neuropharmacology, neurohistochemistry and cell biology of neural cells.
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