AROMATIC L-AMINO ACID DECARBOXYLASE MODULATION

芳香族 L-氨基酸脱羧酶调节

• 批准号: 3382877
• 负责人: NORTON H NEFF
• 金额: $ 13.84万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3382877
• 关键词: aging; alpha adrenergic receptor; aromatic L aminoacid decarboxylase; decarboxylase inhibitor; dopamine; enzyme induction /repression; enzyme mechanism; enzyme substrate; gel electrophoresis; immunocytochemistry; inhibitor /antagonist; laboratory rabbit; laboratory rat; neurotransmitters; photobiology; protein purification; pyridoxal phosphate; retina; stimulant /agonist

Aromatic L-amino acid decarboxylase (AAAD) is the second enzyme in the sequence leading to the formation of catecholamines. It is not considered to be rate-limiting and Until now' there is no evidence for enzyme modulation in vivo. In a model system of CNS dopaminergic neurons (rat retinal dopaminergic neurons) it was observed that AAAD is apparently modulated in vivo by neuronal activity and by drugs that 'interact with neurotransmitter receptors. When rats were placed in a lighted environment from the dark there was a slow rise of AAAD activity over about 3 hours. Activity plateau at about 2 to 3 times the activity found in the dark. Kinetic analysis of AAAD activity revealed an increase of Vmax in light. In addition, the rise was blocked by pretreatment with cycloheximide. These observations suggest that there is induction of AAAD or of a factor(s) needed for enzyme activity. When the lights were turned off, AAAD activity fell rapidly at first and then slowly. Mixing homogenates from animals killed in the light and dark resulted in AAAD activity values similar to dark activity, suggesting that an endogenous inhibitor(s) plays a role in enzyme modulation. Furthermore, administering D-1 dopamine (DA) or alpha-2 adrenergic receptor antagonists to rats in the dark resulted in enhancement of AAAD activity. Conversely, D-1 or alpha-2 receptor agonist administration suppressed AAAD activity in the light. We now seek support to investigate these findings in more detail and to use the information gained in the retinal model system to investigate the enzyme of brain. These studies will change our concepts about neuronal AAAD and provide insight into the mechanism of action of psychoactive drugs.

芳香族L-氨基酸脱羧酶（AAAD）是该酶中的第二种酶。 导致儿茶酚胺形成的顺序。它不被认为 到目前为止，没有证据表明酶 体内调制。在CNS多巴胺能神经元（大鼠）的模型系统中， 视网膜多巴胺能神经元），观察到AAAD明显 在体内由神经元活动和与之相互作用的药物调节 神经递质受体当老鼠被放在一个有光的环境中时， 从黑暗开始，AAAD活性在约3小时内缓慢上升。 在黑暗中发现的活性的约2至3倍处活性稳定。 AAAD活性的动力学分析表明，在光的Vmax增加。 此外，用放线菌酮预处理可以阻断这种上升。 这些观察结果表明，诱导AAAD或 酶活性所需的因素。当灯关上的时候， AAAD活性起初迅速下降，然后缓慢下降。混合匀浆 在光照和黑暗中处死的动物的AAAD活性值 类似于暗活性，表明内源性抑制剂起作用， 在酶调节中的作用。此外，给予D-1多巴胺（DA） 或α-2肾上腺素能受体拮抗剂， 加强AAAD活动。相反，D-1或α-2受体激动剂 有鉴于此，政府抑制了AAAD的活动。我们现在寻求支持 更详细地调查这些发现， 在视网膜模型系统中获得了用于研究脑酶的结果。 这些研究将改变我们对神经元AAAD的概念， 深入了解精神药物的作用机制。