Cardiac (Pro)Renin Receptors: Functional Properties and Potential Significance

Abstract

In many tissues, local angiotensin generation depends on uptake of circulating renin andlor prorenin. Such uptake involves both diffusion into the interstitial space and binding to (pro)renin receptors. This review describes the current status of cardiac (pro)renin receptors, and focusses on their potential significance. (Pro)renin receptors bind both renin and prorenin, and prorenin undergoes a confonnational change ('non-proteolytic' activation) following binding, thereby allowing cell surface angiotensin generation with both renin and prorenin. Renin and prorenin binding also induced direct, angiotensinindependent effects (e.g., ERK112 activation), suggesting that renin and prorenin may act as agonists. Finally, under certain conditions binding resulted in internalization of renin and prorenin. Internalized renin and prorenin were either degraded or, in the case of unglycosylated prorenin, contributed to intracellular angiotensin generation. Taken together, (pro)renin receptors could provide an important new drug target, allowing selective interference with angiotensin production at tissues sites andor direct (pro)renin-induced effects.