Korean J Physiol Pharmacol.  2002 Feb;6(1):21-26.

Transport of Tetraethylammonium in Renal Cortical Endosomes of Cadmium-Intoxicated Rats

• Park HS
• Kim KR
• Park YS

Abstract

Effects of cadmium (Cd) intoxication on renal endosomal accumulation of organic cations (OC ) were studied in rats using 14C-tetraethylammnium (TEA) as a substrate. Cd intoxication was induced by s.c. injections of 2 mg Cd/kg/day for 2-3 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.

Keyword

Cadmium; Kidney; Endosome; Organic cation; H -ATPase; H /TEA antiport

MeSH Terms

Animals
Biological Transport, Active
Cadmium
Cations
Citrus sinensis
Endosomes*
Filtration
Fluorescence
Ion Transport
Ions
Kidney
Proton-Motive Force
Rats*
Tea
Tetraethylammonium*
Cadmium
Cations
Ions
Tea
Tetraethylammonium