Molecular regulation of the type 1 angiotensin receptor

Funded Activity Summary

Angiotensin II is a hormone made in our bodies in response to a decrease in blood pressure (or salt in our bloodstream). It causes our blood vessels to constrict, makes us thirsty, and induces salt and fluid retention via an effect on the kidneys, thereby increasing blood pressure. In some cardiovascular diseases, the generation of angiotensin II or our sensitivity to this hormone is elevated. It is therefore crucial that we understand how angiotensin II works and how its actions in the body are mediated. For angiotensin II to act it must first bind to a receptor. Receptors are proteins and behave like locks that are opened by the hormone keys. Thus, cellular receptors for angiotensin II are engaged and activated by increases in angiotensin II in our blood. These receptors then produce signals which initiate a response (e.g. constriction of a blood vessel). Subsequently, the receptors are switched-off to prevent over-stimulation. The experiments proposed in this application continue our investigations into how angiotensin II receptors are switched-on and -off. A major way for receptors to be turned on is for them to interact with other cellular proteins, although we know only some of these interactions for the angiotensin receptor. Receptors are turned off by being ear-marked by a modification known as phosphorylation; these modified receptors are then bound by proteins termed arrestins, which as indicated by their name, play a role in preventing further receptor signalling. These arrestins also help to remove activated receptors from the cell surface to the inside of the cell. This application proposes new technologies to investigate the spectrum of proteins recruited to the angiotensin receptor and the role of arrestins in switching receptors on and off. Results from these studies will further our understanding of angiotensin II receptors and their role in cardiovascular control.

Funded Activity Details

Start Date: 01-01-2007

End Date: 01-01-2009

Funding Scheme: NHMRC Project Grants

Funding Amount: $695,440.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Pharmacology and Pharmaceutical Sciences

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

G protein-coupled receptors | angiotensin | arrestin | blood pressure regulation | cardiovascular disease and hypertension | molecular basis of disease | molecular pharmacology | pharmacology | receptor trafficking

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