TRANSPORT OF THE GLUTATHIONE-METHYLMERCURY COMPLEX ACROSS LIVER CANALICULAR MEMBRANES ON REDUCED GLUTATHIONE CARRIERS
Dutczak, WJ; Ballatori, N
| HERO ID | 2305122 |
|---|---|
| In Press | No |
| Year | 1994 |
| Title | TRANSPORT OF THE GLUTATHIONE-METHYLMERCURY COMPLEX ACROSS LIVER CANALICULAR MEMBRANES ON REDUCED GLUTATHIONE CARRIERS |
| Authors | Dutczak, WJ; Ballatori, N |
| Journal | Journal of Biological Chemistry |
| Volume | 269 |
| Issue | 13 |
| Page Numbers | 9746-9751 |
| Abstract | The mechanism responsible for the transport of the glutathione-methylmercury complex (CH3HgSG) across liver canalicular membranes into bile was investigated. Uptake of radiolabeled CH3HgSG by canalicular liver plasma membranes (cLPM) isolated from Sprague-Dawley-rats was dependent upon time and temperature. To reduce nonspecific binding of the complex by the membrane, S-(2,4-dinitrophenyl)glutathione was included in the test solutions. Increasing internal medium osmolarity and extrapolation to infinite osmolarity indicated that 50% of the measured complex in cLPM was due to nonspecific membrane binding. Uptake of the CH3HgSG complex was not affected by the replacement of a sodium-chloride gradient with gradients of potassium-chloride or lithium-chloride. Addition of ATP had no effect on CH3HgSG uptake. A significant increase in CH3HgSG uptake was detected when valinomycin was included in an external medium containing 100 millimolar (mM) potassium-gluconate. Uptake of tritiated glutathione (GSH) was also increased under these conditions. Concentration dependent increases in the initial rates of CH3HgSG uptake followed Michaelis-Menten kinetics for substrate concentrations from 5 micromolar to 5 millimolar. Uptake of the CH3HgSG complex was inhibited by GSH, its S-methyl, S-ethyl, S-butyl, S-hexyl, S-octyl, and S-dinitrophenyl conjugates as well as by ophthalmic acid. Uptake was not effected by oxidized glutathione (GSSG), bile acids, amino acids or P-glycoprotein inhibitors. Competitive inhibition of CH3HgSG uptake by GSH was demonstrated by kinetic studies. Preloading of cLPM with CH3HgSG or GSH significantly increased uptake of CH3HgSG. The authors conclude that CH3HgSG and GSH share canalicular transport carriers that are responsible for the elimination of methylmercury (22967926) via bile excretion. |
| Pmid | 8144567 |
| Wosid | WOS:A1994NE05300056 |
| Is Certified Translation | No |
| Dupe Override | 2305122 |
| Is Public | Yes |
| Language Text | English |