EFFECT OF NAFAMOSTAT MESILATE ON NA+ AND K+ TRANSPORT-PROPERTIES IN THE RABBIT CORTICAL COLLECTING DUCT

1 To determine the mechanism(s) of hyperkalemia caused by nafamostat mesilate (NM), a serine-protease inhibitor, we investigated the effects of the drug on Na+ and K+ transport properties of the collecting duct (CD) cell in the isolated and perfused cortical collecting duct from rabbit kidneys. 2 NM at 10(-4) M in the lumen, hyperpolarized the apical membrane in parallel with increases in transepithelial resistance (RT) and fractional apical membrane resistance (fR(A)). 3 These effects were completely inhibited by pretreatment with 50 mum luminal amiloride, whereas they were not affected by luminal addition of 2 mm Ba2+. 4 NM at 10(-4) M in the bath slightly but significantly depolarized the basolateral membrane without any changes in R(T) or fR(A), although NM at 10(-5) M in the bath had no effect on the electrical parameters. 5 It is concluded that NM mainly acts on the apical membrane of the CD cell and inhibits the amiloride-sensitive Na+ conductance in the apical membrane.