000165690 001__ 165690
000165690 005__ 20260113234334.0
000165690 0247_ $$2doi$$a10.1016/j.taap.2008.05.026
000165690 0248_ $$2sideral$$a66560
000165690 037__ $$aART-2008-66560
000165690 041__ $$aeng
000165690 100__ $$aVilla-Bellosta, R.
000165690 245__ $$aRole of Rat sodium/phosphate Cotransporters in the Cell Membrane Transport of Arsenate
000165690 260__ $$c2008
000165690 5060_ $$aAccess copy available to the general public$$fUnrestricted
000165690 5203_ $$aInorganic arsenate (AsV) is a common contaminant of underground water. Following oral exposure, it is assumed that AsV is distributed and crosses cell membranes through inorganic phosphate (Pi) transporters. We have tested this hypothesis by studying the inhibition of rat Na/Pi cotransporters by AsV in Xenopus laevis oocytes and in several rat tissues. The ubiquitously expressed type III Pi transporters (PiT-1 and PiT-2) showed a low affinity for AsV (Ki ~ 3.8 mM), similar to the Pi transport system in aortic vascular smooth muscle cells (Ki 1.5 mM). The type II renal isoforms, NaPi-IIa and NaPi-IIc, were also poorly inhibited by AsV (Ki ~ 1 mM), similar to the Pi transport from kidney cortex brush-border membrane (BBM) vesicles. Conversely, the high-affinity intestinal transporter, NaPi-IIb, was very efficiently inhibited with a Ki of 51 μM, similar to the Pi transport from intestinal BBM vesicles. Taking into account the 1.1 mM Pi in blood and renal ultrafiltrate, and the nanomolar range of AsV exposures, we have determined that the contribution by Na/Pi cotransporters to AsV membrane transport is negligible, given that 10–15 mM AsV would be necessary in these fluids to be significantly transported. Intestinal transport is an exception, because Pi competition is weak, thereby considering that its concentration in lumen mainly depends on low Pi levels from ingested fresh water, and because AsV very efficiently inhibits Pi intestinal transport. Our data agree with current toxicokinetic knowledge, and they explain the asymmetric excretion of trivalent and pentavalent arsenic species into bile and urine.
000165690 536__ $$9info:eu-repo/grantAgreement/ES/MEC/BFU2016-06284-BFI
000165690 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
000165690 590__ $$a3.364$$b2008
000165690 591__ $$aTOXICOLOGY$$b11 / 74 = 0.149$$c2008$$dQ1$$eT1
000165690 591__ $$aPHARMACOLOGY & PHARMACY$$b54 / 216 = 0.25$$c2008$$dQ1$$eT1
000165690 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000165690 700__ $$0(orcid)0000-0003-3457-323X$$aSorribas,V.$$uUniversidad de Zaragoza
000165690 7102_ $$11000$$2807$$aUniversidad de Zaragoza$$bDpto. Anat.Pat.Med.Leg.For.To.$$cArea Toxicología
000165690 773__ $$g232, 1 (2008), 125-134$$pToxicol. appl. pharmacol.$$tTOXICOLOGY AND APPLIED PHARMACOLOGY$$x0041-008X
000165690 8564_ $$s643355$$uhttps://zaguan.unizar.es/record/165690/files/texto_completo.pdf$$yPostprint
000165690 8564_ $$s613827$$uhttps://zaguan.unizar.es/record/165690/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000165690 909CO $$ooai:zaguan.unizar.es:165690$$particulos$$pdriver
000165690 951__ $$a2026-01-13-22:06:01
000165690 980__ $$aARTICLE