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 (fRA). 3. These effects were completely inhibited by pretreatment with 50 microM 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 RT or fRA, 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.
Muto
S
S
Department of Nephrology, Jichi Medical School, Tochigi, Japan.
Imai
M
M
Asano
Y
Y
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001550:Benzamidines; D001693:Biological Transport, Active / Q000187:drug effects; D004594:Electrophysiology; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008839:Microelectrodes; D011188:Potassium / Q000378:metabolism*; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*
D001550:Benzamidines; D006146:Guanidines; D015842:Serine Proteinase Inhibitors; D001464:Barium; D000584:Amiloride; D012964:Sodium; D011188:Potassium; C032855:nafamostat