Inhibition of P-type ATPases by [(dihydroindenyl)oxy]acetic acid (DIOA), a K+ -Cl- cotransporter inhibitor.
[(Dihydroindenyl)oxy]acetic acid (DIOA) has been used as a potent inhibitor of K+ -Cl- cotransporter (IC(50)=10 microM). Here we found that DIOA inhibited activities of P-type ATPases such as dog kidney Na+,K+-ATPase (IC(50)=53 microM), hog gastric H+,K+-ATPase (IC(50)=97 microM) and rabbit muscle Ca(2+)-ATPase (IC(50)=127 microM). 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 microM) and the exogenous H+,K+-ATPase (IC(50)=75 microM). 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 microM) 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.
Fujii
Takuto
T
Department of Pharmaceutical Physiology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Ohira
Yuta
Y
Itomi
Yasuo
Y
Takahashi
Yuji
Y
Asano
Shinji
S
Morii
Magotoshi
M
Takeguchi
Noriaki
N
Sakai
Hideki
H
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology*; D054328:Proton Pump Inhibitors; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013552:Swine; D027981:Symporters / Q000037:antagonists & inhibitors*; D000096922:K Cl- Cotransporters
D000085:Acetates; D004791:Enzyme Inhibitors; D007192:Indenes; D054328:Proton Pump Inhibitors; D000254:Sodium-Potassium-Exchanging ATPase; D027981:Symporters; D000096922:K Cl- Cotransporters; C095651:((2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy)acetic acid