Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0030305 (
pancreatitis
)
16,014
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A serine protease,
prostasin
, has been shown to stimulate the activity of amiloride-sensitive sodium channels (ENaC). Prostasin is a glycosylphosphatidylinositol-anchored protein that is found free in physiologic fluids and tissue culture medium, but the mechanism by which
prostasin
is secreted from the cells has not been elucidated. The current studies found that serine protease inhibitor aprotinin blocked the secretion of
prostasin
in a mouse cortical collecting duct (CCD) cell line (M-1 cells). A synthetic serine protease inhibitor, nafamostat mesilate (NM), which is commonly used for the treatment of
pancreatitis
and disseminated intravascular coagulation in Japan, also inhibited the secretion of
prostasin
in M-1 cells. Continuous infusion of NM into rats resulted in a substantial decrease in urinary
prostasin
and urinary sodium excretion. p-guanidinobenzoic acid and 6-amidino-2-naphtol, catalytically inactive metabolites of NM, had no effect on
prostasin
secretion both in M-1 cells and in rats. These findings suggest that a serine protease-sensitive mechanism is involved in the secretion of
prostasin
in vitro as well as in vivo. Potassium secretion in the CCD is tightly linked to sodium reabsorption through EnaC; therefore, NM-induced decrease in
prostasin
secretion and subsequent inhibition of ENaC activity could account for the side effects of hyponatremia and/or hyperkalemia that are found sometimes in patients treated with NM. The results indicate an important role for
prostasin
in sodium reabsorption in the kidney under pathophysiologic conditions.
...
PMID:Inhibition of prostasin secretion by serine protease inhibitors in the kidney. 1250 33
