Abstract

This work is directed towards the purification and characterization of the GABA receptor/benzodiazepine receptor/C1- channel complex from mammalian brain. For this purpose monoclonal antibodies and antisera to specific protein components of the complex will be used. Monoclonal antibodies and antisera have been raised recently in our laboratory. New antibodies to the complex will be also prepared including anti-idiotypic antibodies to the benzodiazepine receptor. This study is aiming: i) to determine the composition, distribution and specificity of the subunits in the receptor complex isolated from various regions of the mammalian brain, and ii) to study the dynamics of the synthesis, glycosylation, assembly and degradation of the subunits by neurons in culture. These studies should be relevant i) toward understanding the biological effects of benzodiazepines in molecular terms and the role of GABA and benzodiazepine receptors in mental health and disease (anxiety, epilepsy, etc.) and ii) for the development of new therapeutic strategies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS017708-07
Application #
3397775
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1981-07-01
Project End
1989-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
State University New York Stony Brook
Department
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794

  Publications

Li, M; De Blas, A L (1997) Coexistence of two beta subunit isoforms in the same gamma-aminobutyric acid type A receptor. J Biol Chem 272:16564-9
Gutierrez, A; Khan, Z U; Miralles, C P et al. (1997) GABAA receptor subunit expression changes in the rat cerebellum and cerebral cortex during aging. Brain Res Mol Brain Res 45:59-70
Khan, Z U; Gutierrez, A; De Blas, A L (1996) The alpha 1 and alpha 6 subunits can coexist in the same cerebellar GABAA receptor maintaining their individual benzodiazepine-binding specificities. J Neurochem 66:685-91
Gutierrez, A; Khan, Z U; Ruano, D et al. (1996) Aging-related subunit expression changes of the GABAA receptor in the rat hippocampus. Neuroscience 74:341-8
Khan, Z U; Gutierrez, A; Mehta, A K et al. (1996) The alpha 4 subunit of the GABAA receptors from rat brain and retina. Neuropharmacology 35:1315-22
Khan, Z U; Gutierrez, A; Miralles, C P et al. (1996) The gamma subunits of the native GABAA/benzodiazepine receptors. Neurochem Res 21:147-59
Gutierrez, A; Khan, Z U; Miralles, C P et al. (1996) Altered expression of gamma 2L and gamma 2S GABAA receptor subunits in the aging rat brain. Brain Res Mol Brain Res 35:91-102
De Blas, A L (1996) Brain GABAA receptors studied with subunit-specific antibodies. Mol Neurobiol 12:55-71
Fernando, L P; Khan, Z U; McKernan, R M et al. (1995) Monoclonal antibodies to the human gamma 2 subunit of the GABAA/benzodiazepine receptors. J Neurochem 64:1305-11
Fernando, L P; Khan, Z U; De Blas, A L (1995) Antibodies to the rat beta 3 subunit of the gamma-aminobutyric acid A receptors. Brain Res Mol Brain Res 28:94-100

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