Organic Anion Transport and Action of γ-Glutamyl Transpeptidase in Kidney Linked Mechanistically to Renal Tubular Uptake of Inorganic Mercury

Abstract

In the present study, the roles of renal tubular γ-glutamyl transpeptidase and renal organic anion transport on the renal uptake and accumulation and intrarenal distribution of injected inorganic mercury were investigated. The renal (and general) disposition of injected inorganic mercury (Hg²⁺) was evaluated in control rats, rats pretreated with two 10 mg/kg doses of acivicin, rats pretreated with a 10 mmol/kg dose of p-aminohippurate (PAH), and rats pretreated with both acivicin and PAH. The dose(s) of acivicin were used to inhibit the activity of renal γ-glutamyl transpeptidase to a near maximal level and the dose of PAH (which is a water-soluble organic anion) was used to competitively inhibit the renal organic anion transport system to a near maximal level. Dispositional data were obtained at both 1 and 24 hr after a nontoxic, 0.5 μmol/kg iv dose of mercuric chloride had been administered. Radiolabeled inorganic mercury (²⁰³Hg²⁺) was added to the injection solution containing the mercuric chloride to make it possible to quantitate the accumulation and disposition of mercury using standard isotopic methods. The renal concentration and content of mercury were significantly lower in the rats pretreated with either acivicin or PAH than in the control rats at both times after the injection of inorganic mercury. Pretreatment with acivicin mainly affected the content of mercury in the renal cortex, while pretreatment with PAH affected the content of mercury in both the renal cortex and the outer stripe of the outer medulla. Interestingly, the renal concentration and content of mercury in the rats pretreated with both acivicin and PAH were significantly lower than in any of the other three groups at both times after injection of inorganic mercury. Evaluation of the intrarenal distribution of mercury indicated that the renal cortex was the main zone in which the uptake of mercury was significantly affected by both acivicin and PAH. The findings from this study indicate that the renal tubular uptake of administered inorganic mercury is linked both to the transport of organic anions and to the action of γ-glutamyltransferase. Thus, at least two mechanisms appear to be involved in the renal tubular uptake of inorganic mercury.