Abstract

Monoamine oxidase (MAO) is an important degradative enzyme in the monoamine neural tracts whose role in psychiatric disease has been the subject of prolonged controversy. The pharmacologic action of MAO inhibitors has been examined in many past studies. Recently, considerable attention has been directed to the mechanism(s) by which other psychotropic drugs affect MAO, since neuroleptic drugs have been reported in several studies to alter platelet MAO activities in psychiatric patients. This proposal focuses on the origins of the functional difference between the two forms of the enzyme (MAO A and B), which oxidize monoamine neurotransmitters with varying efficiencies and respond differently to inhibitory drugs and hormones. We propose to adapt methodologies which have been applied with success in basic studies of cell systems to examine the endogenous and exogenous factors which control levels of MAO A and B activity and concentration in human tissues. The effects of drugs and hormones on in vivo and in vitro MAO synthetic systems will be examined in the light of genetic controls on protein structure and synthesis and mechanisms which regulate the expression of MAO A and B genes in human cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019543-03
Application #
3399619
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1983-04-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1987-03-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555

  Publications

Denney, R M (1995) The promoter of the human monoamine oxidase A gene. Prog Brain Res 106:57-66
Denney, R M; Sharma, A; Dave, S K et al. (1994) A new look at the promoter of the human monoamine oxidase A gene: mapping transcription initiation sites and capacity to drive luciferase expression. J Neurochem 63:843-56
Riley, L A; Denney, R M (1991) Problems with the measurement of monoamine oxidase A protein concentration in mitochondrial preparations. Revised molecular activities and implications for estimating ratios of MAO A:MAO B molecules from radiochemical assay data. Biochem Pharmacol 42:1953-9
Riley, L A; Waguespack, M A; Denney, R M (1989) Characterization and quantitation of monoamine oxidases A and B in mitochondria from human placenta. Mol Pharmacol 36:54-60
Denney, R M; Riley, L (1988) Characterization of MAO A and MAO B in human placental mitochondria by activity, immunoblotting and radioimmunoassay with monoclonal antibodies and active site labeling with 3H-pargyline. Pharmacol Res Commun 20 Suppl 4:1-5
Thorpe, L W; Westlund, K N; Kochersperger, L M et al. (1987) Immunocytochemical localization of monoamine oxidases A and B in human peripheral tissues and brain. J Histochem Cytochem 35:23-32
Rose, R M; Castellani, S; Boeringa, J A et al. (1986) Platelet MAO concentration and molecular activity: II. Comparison of normal and schizophrenic populations. Psychiatry Res 17:141-51
Fritz, R R; Abell, C W; Denney, R M et al. (1986) Platelet MAO concentration and molecular activity: I. New methods using an MAO B-specific monoclonal antibody in a radioimmunoassay. Psychiatry Res 17:129-40
Kochersperger, L M; Parker, E L; Siciliano, M et al. (1986) Assignment of genes for human monoamine oxidases A and B to the X chromosome. J Neurosci Res 16:601-16
Kochersperger, L M; Waguespack, A; Patterson, J C et al. (1985) Immunological uniqueness of human monoamine oxidases A and B: new evidence from studies with monoclonal antibodies to human monoamine oxidase A. J Neurosci 5:2874-81

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