REGULATION OF THE CATECHOLAMINE BIOSYNTHETIC ENZYMES

这项建议试图研究监管的几个方面的重要 神经递质酶，它们的反应成分，以及 它们会刺激细胞，进而引发关键的细胞事件。这个 应用程序是一种竞争性的续订，以支持我们在这些领域正在进行的工作。 这项工作的主旨是调节神经递质酶和 从细胞、代谢和遗传角度看受体。这项工作将是 在体内和体外都在大脑和肾上腺中进行。要将项目 进行的是：(A)苯乙醇胺N-甲基转移酶的调节 糖皮质激素、S-腺苷甲硫氨酸和内脏器官的营业额 神经递质；(B)S-腺苷甲硫氨酸水平的调节 通过糖皮质激素和其他因素；(C)羟基吲哚的调节 糖皮质激素对O-甲基转移酶(HIOMT)的代谢；(D)调节 抗坏血酸在体内降解多巴胺β-羟基酶(DBH)； 木霉PNMT和DBH降解酶的分离及性质 活体；(F)胸径周转的遗传调控；(G)PNMT的遗传学 小鼠的反应性；(H)5-羟色胺、5-羟色胺酶和 近交系小鼠的5-羟色胺受体及(1)单抗的研制 对PNMT、DBH、HIOMT及S-腺苷蛋氨酸代谢酶的影响。

This proposal seeks to study several aspects of the regulation of important neurotransmitter enzymes, their reaction constituents, and the receptors which they stimulate and which in turn initiate critical cellular events. The application is a competing renewal to support our ongoing work in these areas. The main thrust of the work is regulation of neurotransmitter enzymes and receptors from a cellular, metabolic and genetic standpoint. The work will be carried out in brain and in adrenal both in vivo and in vitro. The projects to be conducted are: (A) regulation of phenylethanolamine N-methyltransferase (PNMT) turnover by glucocorticoids, by S-adenosylmethionine and by splanchnic neuronal neurotransmitters; (B) regulation of S-adenosylmethionine (SAM) levels by glucocorticoids and other factors; (C) regulation of hydroxyindole O-methyltransferase (HIOMT) turnover by glucocorticoids; (D) regulation of dopamine beta-hydroxylase (DBH) proteolysis in vivo by ascorbic acid; (E) isolation and characterization of the proteases which degrade PNMT and DBH in vivo; (F) genetic regulation of DBH turnover; (G) genetics of PNMT responsiveness in mice; (H) genetics of serotonin, serotonin enzymes and serotonin receptors in inbred mice and (1) deveopment of monoclonal antibodies to PNMT, DBH, HIOMT and the enzymes of S-adenosylmethionine metabolism.