PMID- 10702366 OWN - NLM STAT- MEDLINE DCOM- 20000410 LR - 20131121 IS - 0041-008X (Print) IS - 0041-008X (Linking) VI - 163 IP - 3 DP - 2000 Mar 15 TI - Chloride secretion in kidney distal epithelial cells (A6) evoked by cadmium. PG - 267-78 AB - The effect of Cd(2+) on chloride secretion was examined in A6 renal epithelia cells by chloride-sensitive fluorescence (SPQ probe) and by the short-circuit-current (I(sc)) technique. Depleting the cells of Cl(-) suggests that the Cd(2+)-activated I(sc) (DeltaI(sc(Cd))) is dependent on the presence of Cl(-) ions. Among the Cl(-)-channel inhibitors the fenemates, flufenamic acid (FFA) and niflumic acid (NFA), and 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) significantly lowered DeltaI(sc(Cd)) compared with control level. In SPQ-loaded A6 cells, Cd(2+) evoked an increase in Cl(-) secretion ([DeltaCl(-)](Cd)), which significantly exceeded the basal Cl(-) transport and was blockable by FFA and NFA. The closely related metals, Zn(2+) or Ni(2+), were also able to activate Cl(-) secretion. Preexposure of Zn(2+) or Ni(2+) completely prevented [DeltaCl(-)](Cd), suggesting that Zn(2+) and Ni(2+) probably use similar mechanisms. Like Cd(2+), thapsigargin (TG), an inhibitor of intracellular Ca(2+)-ATPase and the Ca(2+)-ionophore A23187, induced an increase in I(sc). Moreover, TG and Cd(2+) were able to neutralize the responses of the counterparts as also observed in I(sc) measurements, which indicates that Cd(2+) activates Cl(-) secretion in a Ca(2+)-dependent manner. Hence, this study supports the idea that basolateral Cd(2+) (possibly also Zn(2+) and Ni(2+)), probably through a Ca(2+)-sensing receptor, causes calcium mobilization that activates apical fenemate-sensitive chloride channels leading to chloride secretion in A6 cells. CI - Copyright 2000 Academic Press. FAU - Faurskov, B AU - Faurskov B AD - Grenaa Central Hospital, Sygehusuej 6, 8500, Grenaa, Denmark. bf@get2net.dk FAU - Bjerregaard, H F AU - Bjerregaard HF LA - eng PT - Journal Article PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 0 (Chloride Channels) RN - 0 (Chlorides) RN - 0 (Fluorescent Dyes) RN - 0 (Metals) RN - 00BH33GNGH (Cadmium) RN - SY7Q814VUP (Calcium) SB - IM MH - Algorithms MH - Animals MH - Cadmium/*toxicity MH - Calcium/metabolism MH - Cell Line MH - Chloride Channels/antagonists & inhibitors/metabolism MH - Chlorides/*metabolism MH - Electrophysiology MH - Epithelial Cells/drug effects/metabolism MH - Fluorescent Dyes MH - Kidney/cytology/drug effects/*metabolism MH - Metals/toxicity MH - Patch-Clamp Techniques MH - Spectrometry, Fluorescence MH - Xenopus laevis EDAT- 2000/03/07 09:00 MHDA- 2000/04/15 09:00 CRDT- 2000/03/07 09:00 PHST- 2000/03/07 09:00 [pubmed] PHST- 2000/04/15 09:00 [medline] PHST- 2000/03/07 09:00 [entrez] AID - S0041-008X(99)98852-X [pii] AID - 10.1006/taap.1999.8852 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 2000 Mar 15;163(3):267-78. doi: 10.1006/taap.1999.8852.