A novel mechanism for the maintenance of catecholamine synthesis

维持儿茶酚胺合成的新机制

• 批准号: nhmrc : 351118
• 负责人: A/Pr Phillip Dickson
• 金额: $ 23.75万
• 依托单位: The University of Newcastle
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/novel-mechanism-maintenance-catecholamine-synthesis/100301
• 关键词: novel; mechanism; maintenance; catecholamine; synthesis

Stress causes an acute response that prepares us for flight or a fight and an adaptive response that requires days to establish. The catecholamines, including adrenaline, noradrenaline and dopamine are critical to both the acute and adaptive stress responses. They are secreted from cells at the level of the nervous system and the adrenal gland. We all respond differently to stress and if we do not cope we can become hypertensive or depressed. These pathologies require drug management and the drugs all affect the catecholamine systems. Tyrosine hydroxylase controls catecholamine synthesis and it is activated in both the acute and adaptive phases of the stress response in order to replace catecholamines that have been secreted. Tyrosine hydroxylase is activated by protein phosphorylation in the acute phase and by the synthesis of new tyrosine hydroxylase in the adaptive phase. We have now discovered an additional and novel phase that we refer to as sustained tyrosine hydroxylase activation. This phase spans at least the period between the acute (mins) and adaptive phases (days). It involves the sustained phosphorylation of tyrosine hydroxylase and its mechanism appears to differ from the other two phases. In this project we will answer three questions. Does sustained tyrosine hydroxylase activation: 1 Occur in response to many stimuli and in many catecholamine cell types? 2 Occur by a single mechanism, different to the other phases, in all circumstances? 3 Play a role in the control of blood pressure and depression? This project will provide fundamental data about the mechanisms and consequences of sustained tyrosine hydroxylase activation, which is a part of the stress response not previously discovered. The data may impact on the way we design drugs to control stress responses, including antidepressants and antihypertensives.

压力会引起一种急性反应，让我们为逃跑或战斗做好准备，而适应性反应则需要几天的时间来建立。儿茶酚胺，包括肾上腺素、去甲肾上腺素和多巴胺，对急性和适应性应激反应都至关重要。它们由神经系统和肾上腺水平的细胞分泌。我们对压力的反应各不相同，如果我们不应对压力，我们可能会患上高血压或抑郁症。这些病理需要药物管理，药物都影响儿茶酚胺系统。酪氨酸羟化酶控制儿茶酚胺的合成，它在应激反应的急性和适应阶段都被激活，以取代已经分泌的儿茶酚胺。酪氨酸羟化酶在急性期由蛋白磷酸化激活，在适应期由新的酪氨酸羟化酶合成激活。我们现在已经发现了一个额外的和新的阶段，我们称之为持续酪氨酸羟化酶激活。这个阶段至少在急性期（分钟）和适应期（天）之间。它涉及酪氨酸羟化酶的持续磷酸化，其机制似乎不同于其他两个阶段。在这个项目中，我们将回答三个问题。持续的酪氨酸羟化酶激活：1是否发生在对许多刺激和许多儿茶酚胺细胞类型的反应中？在所有情况下，以不同于其他阶段的单一机制发生？在控制血压和抑郁方面发挥作用？该项目将提供关于持续酪氨酸羟化酶激活的机制和后果的基础数据，这是以前未发现的应激反应的一部分。这些数据可能会影响我们设计药物来控制压力反应的方式，包括抗抑郁药和抗高血压药。