• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.21-26
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• 2002

Effects of cadmium (Cd) intoxication on renal endosomal accumulation of organic cations $(OC^+)$ were studied in rats using $^{14}C-tetraethylammnium$ (TEA) as a substrate. Cd intoxication was induced by s.c. injections of 2 mg Cd/kg/day for $2{\sim}3$ weeks. Renal cortical endosomes were isolated and the endosomal acidification (acridine orange fluorescence change) and TEA uptake (Millipore filtration technique) were assessed. The TEA uptake was an uphill transport mediated by $H^+/OC^+$ antiporter driven by the pH gradient established by $H^+-ATPase.$ In endosomes of Cd-intoxicated rats, the ATP-dependent TEA uptake was markedly attenuated due to inhibition of endosomal acidification as well as $H^+/TEA$ antiport. In kinetic analysis of $H^+/TEA$ antiport, Vmax was reduced and Km was increased in the Cd group. Inhibition of $H^+/TEA$ antiport was also observed in normal endosomes directly exposed to free Cd (but not Cd-metallothionein complex, CdMt) in vitro. These data suggest that during chronic Cd exposure, free Cd ions liberated by lysosomal degradation of CdMt in proximal tubule cells may impair the endosomal accumulation of $OC^+$ by directly inhibiting the $H^+/OC^+$ antiporter activity and indirectly by reducing the intravesicular acidification, the driving force for $H^+/OC^+$ exchange.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.2
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• pp.191-198
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• 1999

This study was undertaken to examine the effect of ethanol on $Na^+-dependent$ transport systems (glucose, phosphate, and dicarboxylate) in renal brush-border membrane vesicles (BBMV). Ethanol inhibited $Na^+-dependent$ uptakes of glucose, phosphate, and succinate in a dose-dependent manner, but not the uptakes of $Na^+-dependent.$ The $H^+/TEA$ antiport was reduced by 8% ethanol. Kinetic analysis showed that ethanol caused a decrease in $V_{max}$ of three transport systems, leaving $K_m$ values unchanged. Ethanol decreased phlorizin binding, which was closely correlated with the decrease in $V_{max}$ of $Na^+-glucose$ uptake. These results indicate that ethanol inhibits $Na^+-dependent$ uptakes of glucose, phosphate, and dicaboxylate and that the reduction in $V_{max}$ of $Na^+-glucose$ uptake is caused by a decrease in the number of active carrier proteins in the membrane.