(Pro)renin receptor as a new drug target

Curr Pharm Des. 2011 Nov;17(33):3611-21. doi: 10.2174/138161211798220963.

Abstract

Over the last few years, the implication of the (pro)renin receptor [(P)RR] in the pathogenesis of end-organ damage has been shown through many different studies. The (P)RR plays a dual role when stimulated by renin or prorenin as it enhances both cell surface production of angiotensin and stimulates angiotensin-independent intracellular signaling cascades. Since Ichihara's group demonstrated activation of prorenin when it was bound to antibodies targeted against a specific region in the renin prosegment, they designed a complementary decapeptide to this region called the handle region to use as a potential (P)RR blocker (PRRB). The effects of systemic administration of the PRRB on the development and progression of different renal, cardiac and ocular pathologies have been observed and have thus proposed the blocker as a potential new treatment for these afflictions. Conversely, the specificity of the PRRB has been questioned as conflicting results have been reported in the literature. A recent study has described a new high affinity binding site for renin and prorenin to the (P)RR called the hinge region. Hence, although there is great promise in the (P)RR potential as a therapeutic target, still much research is required to better identify adequate blockers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cardiovascular Agents / pharmacology*
  • Cardiovascular Diseases / drug therapy
  • Disease Models, Animal
  • Humans
  • Prorenin Receptor
  • Receptors, Cell Surface / drug effects*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology
  • Renin / blood
  • Signal Transduction / drug effects
  • Vacuolar Proton-Translocating ATPases / metabolism

Substances

  • Cardiovascular Agents
  • Receptors, Cell Surface
  • Renin
  • Vacuolar Proton-Translocating ATPases
  • Prorenin Receptor