Pharmacological study of the angiotensin-(1-7) bindingsites in target cells of the renin-angiotensin system.

Angiotensin II, the major actor of the renin-angiotensin system, plays a pivotal role in the regulation of the cardiovascular system by increasing blood pressure. It has been shown that angiotensin II is degraded by selective peptidases into different peptide fragments such as angiotensin III, angiotensin IV and angiotensin-(1-7). Several findings suggest that angiotensin-(1-7) may play a significant role as a vasodepressor that opposes the hemodynamic actions of Angiotensin II. The aim of the present project is to investigate by which mechansim angiotensin-(1-7) exerts its effects. It will be investigated whether this peptide binds to a separate receptor. If so, the pharmacological and signalling properties of this putative receptor will be determined in certain target cells of the renin-angiotensin system. subsequently we will measure and characterize the specific binding of [125I]-angiotensin-(1-7) in intact target cells of the renin-angiotensin system. Alternatively we will investigate if angiotensin-(1-7) interacts with known angiotensin receptors (AT1, AT2 or AT4).