The renin receptor: the facts, the promise and the hope

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Abstract
The renin-angiotensin system plays a major role in the control of blood pressure and of salt balance, but it is also involved in physiological and pathological processes, development, inflammation and cardiac hypertrophy. A concept has emerged suggesting that these effects are due to a local activation of the renin-angiotensin system. The search for a receptor of renin was based on the idea that tissue (pro)renin is taken up from the circulation and on data suggesting that renin has cellular effects independent of angiotensin II. Endothelial cells and cardiac myocytes bind (pro)renin via the mannose-6-phosphate receptor, mainly a clearance receptor as no cellular effect has been specifically attributed to prorenin binding. A functional receptor was cloned recently. It mediates intracellular signalling by activating the mitogen activated protein kinases, extracellular signal regulated kinases 1 and 2, and acts as a co-factor by increasing the efficiency of angiotensinogen cleavage by receptor-bound (pro)renin. The receptor is abundantly expressed in heart, brain, placenta and eye, compared with a lower expression in liver and kidney. In normal human kidney and heart, it is localized in the mesangium and in the coronary and kidney artery, associated with smooth-muscle cells and co-localized with renin. This receptor provides a functional role for prorenin and may help to understand the physiological and pathological role of elevated levels of prorenin and of local activation of the renin-angiotensin system. From a practical point of view, it questions the need for a pharmacological compound blocking (pro)renin binding and activity as an alternative to the classical inhibitors of the renin-angiotensin system.