Inhibition of P-type ATPases by [(dihydroindenyl)oxy]acetic acid (DIOA), a K +–Cl − cotransporter inhibitor

• Published in: European journal of pharmacology 2007-04, Vol.560 (2), p.123-126
• Main Authors: Fujii, Takuto, Ohira, Yuta, Itomi, Yasuo, Takahashi, Yuji, Asano, Shinji, Morii, Magotoshi, Takeguchi, Noriaki, Sakai, Hideki
• Format: Article
• Language: English
• Subjects: Acetates - pharmacology; Animals; Biological and medical sciences; DIOA ([(dihydroindenyl)oxy]acetic acid); Dogs; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; H +,K +-ATPase; Indenes - pharmacology; K +–Cl − cotransporter; K Cl- Cotransporters; Medical sciences; Na +,K +-ATPase; Pharmacology. Drug treatments; Proton Pump Inhibitors; Rabbits; Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors; Swine; Symporters - antagonists & inhibitors
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2006.12.031

[(Dihydroindenyl)oxy]acetic acid (DIOA) has been used as a potent inhibitor of K +–Cl − cotransporter (IC 50 = 10 μM). Here we found that DIOA inhibited activities of P-type ATPases such as dog kidney Na +,K +-ATPase (IC 50 = 53 μM), hog gastric H +,K +-ATPase (IC 50 = 97 μM) and rabbit muscle Ca 2+-ATPase (IC 50 = 127 μM). In the membrane preparation of the LLC-PK1 cells stably expressing rabbit gastric H +,K +-ATPase, DIOA inhibited activities of the endogenous Na +,K +-ATPase (IC 50 = 95 μM) and the exogenous H +,K +-ATPase (IC 50 = 75 μM). 5-Nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), a Cl − channel blocker, had no effects on the DIOA-elicited inhibition of the P-type ATPases. These findings suggest that lower concentration of DIOA (< 20–30 μM) should be used for evaluation of the activity of K +–Cl − cotransporter without affecting the activities of coexisting Na +,K +-ATPase and/or H +,K +-ATPase in cells.