Abstract

The purpose of this study is to elucidate DA agonists and antagonists induced changes in pre- and postsynaptic DA neuronal systems. These studies will be focused on the following areas: 1) The mechanisms and activation of TH activity by c-AMP dependent protein kinase systems; 2. The regulation of tyrosine hydroxylase activity by specific DA receptors 3. The purification of enzymes involved in monoamine biosynthesis. The properties of these enzymes will be characterized and purified enzymes will be utilized for production of specific antisera. 4. The biochemical and morphological interaction of the Epinephrine neuronal systems with other monoaminergic systems will be studied. 5. Methods will be developed for characterization and purification of multiple DA receptors. 6. The effect of chronic treatment with DA agonists and antagonists on pre- postsynaptic neuronal systems will be investigated. We hope that the results of our study will provide new insight on biochemical changes which occur during treatments of mental and neurological disorders with DA antagonists and agonists.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH002717-31
Application #
3374540
Study Section
(BPNA)
Project Start
1977-03-01
Project End
1991-02-28
Budget Start
1989-03-01
Budget End
1990-02-28
Support Year
31
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012

  Publications

Dreher, Jean-Claude; Meyer-Lindenberg, Andreas; Kohn, Philip et al. (2008) Age-related changes in midbrain dopaminergic regulation of the human reward system. Proc Natl Acad Sci U S A 105:15106-11
Lew, J Y; Garcia-Espana, A; Lee, K Y et al. (1999) Increased site-specific phosphorylation of tyrosine hydroxylase accompanies stimulation of enzymatic activity induced by cessation of dopamine neuronal activity. Mol Pharmacol 55:202-9
Xu, Z Q; Lew, J Y; Harada, K et al. (1998) Immunohistochemical studies on phosphorylation of tyrosine hydroxylase in central catecholamine neurons using site- and phosphorylation state-specific antibodies. Neuroscience 82:727-38
Haycock, J W; Lew, J Y; Garcia-Espana, A et al. (1998) Role of serine-19 phosphorylation in regulating tyrosine hydroxylase studied with site- and phosphospecific antibodies and site-directed mutagenesis. J Neurochem 71:1670-5
Harada; Wu, J; Haycock, J W et al. (1996) Regulation of L-DOPA biosynthesis by site-specific phosphorylation of tyrosine hydroxylase in AtT-20 cells expressing wild-type and serine 40-substituted enzyme. J Neurochem 67:629-35
Goldstein, M; Lee, K Y; Lew, J Y et al. (1995) Antibodies to a segment of tyrosine hydroxylase phosphorylated at serine 40. J Neurochem 64:2281-7
Goldstein, M; Deutch, A Y (1992) Dopaminergic mechanisms in the pathogenesis of schizophrenia. FASEB J 6:2413-21
Enz, A; Goldstein, M; Meller, E (1990) Dopamine agonist-induced elevation of striatal acetylcholine: relationship between receptor occupancy and response in normal and denervated rat striatum. Mol Pharmacol 37:560-5
Harada, K; Meller, E; Goldstein, M (1990) Effects of pertussis toxin on inhibition of synaptosomal tyrosine hydroxylase activity by apomorphine. Eur J Pharmacol 188:123-8
Lew, J Y; Zawadzka, H; Feigenblum, D et al. (1990) Regulation and molecular characterization of dopamine D2 receptors in a prolactin-secreting 7315a anterior pituitary tumor. Eur J Pharmacol 188:329-34

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