THE MECHANISM OF EXCRETION OF TRIENTINE FROM THE RAT-KIDNEY - TRIENTINE IS NOT RECOGNIZED BY THE H+ ORGANIC CATION TRANSPORTER

Trientine dihydrochloride is used to treat Wilson's disease by chelati ng copper and increasing its urinary excretion. The mechanism of renal excretion of trientine has been investigated in-vivo and in-vitro. Tr ientine clearance in the rat was significantly faster than creatinine clearance. When trientine and the same number of moles of copper ions were administered simultaneously to the rat, however, trientine cleara nce decreased to almost the same level as the creatinine clearance. To clarify this active excretion system for trientine, the uptake of tri entine and a physiological polyamine compound, spermine, was investiga ted using rat renal brush-border membrane vesicles. Although, because trientine and spermine are organic cations, the H+/organic cation tran sporter is expected to recognize these compounds, neither an outwardly directed H+ gradient nor an inward Na+ gradient stimulated trientine uptake. [C-14]Spermine uptake was, nevertheless, trans-stimulated by b oth unlabelled spermine and trientine and the trans-stimulating effect of spermine on trientine uptake was, furthermore, completely abolishe d by addition of copper ions to the incubation medium. These results s uggest that there is a specific transport system for spermine and trie ntine on the renal brush-border membrane. This transport system contri butes to the secretion of trientine in the kidney proximal tubule but does not recognize the trientine-copper complex.