AROMATIC L-AMINO ACID DECARBOXYLASE MODULATION

芳香族 L-氨基酸脱羧酶调节

• 批准号: 6149402
• 负责人: NORTON H NEFF
• 金额: $ 5万
• 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 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6149402
• 关键词: aging; alpha adrenergic receptor; aromatic L aminoacid decarboxylase; decarboxylase inhibitor; dopamine; dopamine agonists; dopamine antagonists; enzyme activity; enzyme induction /repression; enzyme mechanism; enzyme substrate; gel electrophoresis; immunocytochemistry; laboratory rabbit; laboratory rat; neurotransmitters; photobiology; protein purification; pyridoxal phosphate; retina

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-氨基酸脱羧酶是植物体内的第二种酶。 导致儿茶酚胺形成的序列。它不被认为是 是限速的，到目前为止还没有证据表明有酶 体内的调制。在中枢多巴胺能神经元(大鼠)模型系统中 视网膜多巴胺能神经元)观察到AAAD明显 在体内受神经元活动和药物的调节 神经递质受体。当老鼠被放在有光的环境中时 从黑暗中开始，AAAD的活动在大约3个小时内缓慢上升。 活动平台期大约是在黑暗中发现的活动的2到3倍。 AAAD活性的动力学分析表明，光照下Vmax增加。 此外，环己酰亚胺预处理能抑制这一上升。 这些观察结果表明，存在AAAD的诱导或 酶活性所需的因子(S)。当灯熄灭时， AAAD活动起初迅速下降，然后缓慢下降。混合匀浆 从在光明和黑暗中被杀的动物产生的AAAD活动值 与暗活动相似，表明内源抑制物(S)起作用 在酶的调节中起作用。此外，给予D-1多巴胺(DA) 或α-2肾上腺素能受体拮抗剂在黑暗中给大鼠造成 AAAD活性增强。相反，D-1或α-2受体激动剂 在此情况下，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，并利用这些信息 在视网膜模型系统中获得，以研究大脑的酶。 这些研究将改变我们对神经元AAAD的概念，并提供 深入了解精神活性药物的作用机制。