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Proteolytic activation of the epithelial sodium channel and therapeutic application of a serine protease inhibitor for the treatment of salt-sensitive hypertension

  • Review Article
  • The 36th IUPS Satellite Symposium: The Kidney and Hypertension
  • Published:
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Abstract

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 α, β, and, γ. The dual cleavage of α subunit by furin and γ 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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Authors and Affiliations

  1. Department of Nephrology, Kumamoto University, Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan

    Kenichiro Kitamura & Kimio Tomita

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  1. Kenichiro Kitamura
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  2. Kimio Tomita
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Correspondence to Kenichiro Kitamura.

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Kitamura, K., Tomita, K. Proteolytic activation of the epithelial sodium channel and therapeutic application of a serine protease inhibitor for the treatment of salt-sensitive hypertension. Clin Exp Nephrol 16, 44–48 (2012). https://doi.org/10.1007/s10157-011-0506-1

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  • DOI: https://doi.org/10.1007/s10157-011-0506-1

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