A novel mechanism for the maintenance of catecholamine synthesis

Funded Activity Summary

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.

Funded Activity Details

Start Date: 01-01-2005

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $356,250.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Cellular Nervous System

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Angiotensin II | Brain cell cultures | CNS function | Catecholamines | Control of blood pressure | Mental health | Nervous System | Stress | Stress response | Tyrosine hydroxylase

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