TRANSPORT INTERACTIONS OF DIFFERENT ORGANIC CATIONS DURING THEIR EXCRETION BY THE INTACT RAT-KIDNEY

Organic cations, in addition to being filtrated, are secreted or reabs orbed in the proximal renal tubule whereby they have to pass the contr aluminal and the luminal cell membrane. Interactions with the transpor t of other organic cations can occur at either cell side, leading to i nhibition or stimulation of net secretion or net reabsorption. A quali tative evaluation of such processes is possible by using the in vivo b olus injection of an organic cation as test substance. Measuring its u rinary excretion profile in relation to that of inulin, under control conditions and after application of interfering organic cations, in co mbination with simultaneous registration of its tissue concentration, allows the demonstration of interaction and also the tentative identif ication of the cell side at which interference has taken place. As tes t substance the fluorescent organic cation 4-(4- dimethylaminostyryl)- N-methylpyridinium (4-Di-1-ASP(+);(+) denotes permanent positively-cha rged organic cations was used, having a protein binding of 47% under t he given experimental conditions. As interfering organic cations amilo ride, benzylamiloride, choline(+), cimetidine, and 2-methyl-4-(heptafl uorobutoxy)-N- methylpyridinium(+) were injected. It was found that: ( 1) 4-Di-1-ASP(+) is filtered and net reabsorbed under control conditio ns (fractional excretion 0.54 +/- 0.1). All net secreted interfering s ubstances, except bidirectional transported choline(+), injected simul taneously with 4-Di-1-ASP(+), showed an interference with renal excret ion of net reabsorbed 4-Di-1-ASP(+), by (2) instantaneously increasing its reabsorption, resulting in a 28 to 33% decrease in urinary excret ion, and (3) augmenting its tissue concentration by 19 to 58%. (4) A p rolonged effect of the interfering substrates could be observed after a third injection of 4-Di-1-ASP(+) (without inhibitor) showing an incr eased tissue concentration of 4-Di-1-ASP(+) of 36 to 46%. The complex interfering pattern of the applied organic cations can be explained by a trans-stimulation of 4-Di-1-ASP(+) net reabsorption at the luminal cell side, leading to an increased intracellular content of 4-Di-1ASP( +).