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TYROSINE HYDROXYLASE PHOSPHORYLATION AND SCHIZOPHRENIA

酪氨酸羟化酶磷酸化与精神分裂症

基本信息

批准号：
3428726
负责人：
JOHN W HAYCOCK
金额：
$ 3.39万
依托单位：
LSU HEALTH SCIENCES CENTER
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-09-01 至 1988-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3428726
关键词：
carbamazepine catecholamines clozapine corpus striatum dopamine drug administration rate /duration haloperidol hydroxylation lithium mental disorder chemotherapy phosphorylation protein kinase schizophrenia synaptosomes tyrosine 3 monooxygenase

项目摘要

The long-term objectives of the proposed research are to determine whether alterations in the levels and/or phosphorylation of tyrosine hydroxylase in the brain may be involved the etiology and/or pathogenesis of schizophrenia. In normal animals, activation of dopaminergic neurons results in the secretion of dopamine and a compensatory replenishment of dopamine stores. This replenishment of dopamine stores results from an increase in dopamine biosynthesis, the underlying basis of which is an increase in the catalytic activity of tyrosine hydroxylase, the rate-limiting enzyme in dopamine biosynthesis. One mechanism to increase the activity of tyrosine hydroxylase, described in other catecholamine-containing neurons, is the stimulation-dependent phosphorylation of tyrosine hydroxylase. Abberations in the dopaminergic systems in brain have been previously linked to schizophrenia; however, the exact relationship is as yet unknown. It is the premise of this grant application that alterations either in tyrosine hydroxylase or the protein kinase systems that attend tyrosine hydroxylase may be involved in schizophrenia. The specific objectives of the proposed research are 1.) to describe the regulation of tyrosine hydroxylase phosphorylation in dopaminergic nerve terminals in brain, 2.) to determine protein kinases systems that are involved in this regulation by using peptide mapping, and 3.) to assess the effects of acute and chronic drug treatments that have been shown to be effective in treating schizophrenia in a clinical setting. Specifically, the ability of treatments that cause the release of dopamine from rat, corpus striatum synaptosomes will be evaluated for their ability to increase the phosphorylation of tyrosine hydroxylase. The site-specificity of this phosphorylation will then be used to infer the protein kinase systems involved in this effect. Lastly, acute and chronic treatment of rats with haloperidol, clozapine, lithium chloride, or carbamazepine will be evaluated for their effects upon tyrosine hydroxylase levels, secretagogue- dependent phosphorylation of tyrosine hydroxylase, and the site- specificity of tyrosine hydroxylase phosphorylation.

拟议研究的长期目标是

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Clinical and laboratory correlates of human immunodeficiency virus infection in a cohort of intravenous drug users from New York, NY.

来自纽约州纽约市的一组静脉注射吸毒者中人类免疫缺陷病毒感染的临床和实验室相关性。

DOI：
发表时间：
1992
期刊：
Archives of internal medicine
影响因子：
0
作者：
el-Sadr,W;Goetz,RR;Sorrell,S;Joseph,M;Ehrhardt,A;Gorman,JM
通讯作者：
Gorman,JM

The effect of zidovudine on neuropsychiatric measures in HIV-infected men.

齐多夫定对艾滋病毒感染男性神经精神指标的影响。

DOI：
10.1176/ajp.150.3.505
发表时间：
1993
期刊：
The American journal of psychiatry
影响因子：
0
作者：
Gorman,JM;Mayeux,R;Stern,Y;Williams,JB;Rabkin,J;Goetz,RR;Ehrhardt,AA
通讯作者：
Ehrhardt,AA

Psychological distress and natural killer cells in gay men with and without HIV infection.

感染和未感染艾滋病毒的男同性恋者的心理困扰和自然杀伤细胞。

DOI：
10.1176/ajp.151.10.1479
发表时间：
1994
期刊：
The American journal of psychiatry
影响因子：
0
作者：
Sahs,JA;Goetz,R;Reddy,M;Rabkin,JG;Williams,JB;Kertzner,R;Gorman,JM
通讯作者：
Gorman,JM

Glucocorticoid level and neuropsychiatric symptoms in homosexual men with HIV infection.

感染艾滋病毒的男同性恋者的糖皮质激素水平和神经精神症状。

DOI：
10.1176/ajp.148.1.41
发表时间：
1991
期刊：
The American journal of psychiatry
影响因子：
0
作者：
Gorman,JM;Kertzner,R;Cooper,T;Goetz,RR;Lagomasino,I;Novacenko,H;Williams,JB;Stern,Y;Mayeux,R;Ehrhardt,AA
通讯作者：
Ehrhardt,AA

Psychoneuroimmunology and HIV infection.

心理神经免疫学和艾滋病毒感染。