Corin and the Natriuretic Peptide System

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Natriuresis is the process by which sodium is excreted in the urine; this process is regulated (in part at least) by the natriuretic peptides ANP and BNP (there is also a CNP, which appears to have direct effects on smooth muscle cells. Secreted by many organs (e.g., brain, kidney, and peripheral blood vessels) in response to high blood pressure or hypervolemic states, ANP and BNP peptides bind to a family of receptors (there are three: NPR-A, NPR-B, and NPR-C) where they generally work to decrease lower blood volume and blood pressure.

Like many endocrine peptide hormones, ANP and BNP are synthesized as pre-propeptides; after the signal peptide is removed, an additional proteolytic cleavage event is necessary to activate the hormone. It has recently been determined that this cleavage event is mediated by corin, type of serine protease. Two key pieces of information suggest that corin is highly relevant to the field of nephrology and hypertension:

1. Mice lacking corin develop hypertension as a result of decreased conversion of pro-ANP to active ANP.

2. Human polymorphisms in the corin gene appear to be associated with salt-sensitive hypertension.

Perhaps these insights will lead to new drug therapies for the future…

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