Journal
CLINICAL AND EXPERIMENTAL NEPHROLOGY
Volume 16, Issue 1, Pages 44-48Publisher
SPRINGER
DOI: 10.1007/s10157-011-0506-1
Keywords
Epithelial sodium channel (ENaC); Serine protease; Serine protease inhibitor; Salt-sensitive hypertension
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Proteases are involved in numerous essential biological processes including blood clotting, controlled cell death, and tissue differentiation. Prostasin, a glycosylphosphatidylinositol-anchored serine protease, has been identified as a potential regulator of the epithelial sodium channel (ENaC) function in the kidney, lung, and airways. ENaC is composed of three homologous subunits alpha, beta, and, gamma. The dual cleavage of alpha subunit by furin and gamma subunit by prostasin and furin releases inhibitory segments from ENaC, leading to the channel activation. Protease nexin-1, an endogenous prostasin inhibitor, inhibits ENaC activity through the suppression of prostasin activity, strongly suggesting the possibility that a coordinated regulation of serine proteases and serine protease inhibitors plays a key role in the sodium handling in the kidney. Camostat mesilate (CM), a synthetic serine protease inhibitor, reduced prostasin activity and subsequently decreased ENaC current. Oral administration of CM to Dahl salt-sensitive rats resulted in a significant decrease in blood pressure with an elevation of the urinary sodium/potassium ratio. These findings suggest that synthetic serine protease inhibitors such as CM might represent a new class of antihypertensive drugs in patients with salt-sensitive hypertension.
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