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This article reviewed the transport mechanism of polycationic compounds across rat intestinal and renal cell membranes. The inside-negative diffusion potential stimulated the initial uptake of dicationic compounds into intestinal brush-border membrane vesicles, and a good correlation was observed between lipophilicity and the amount of diffusion potential-dependent transport of the dications. On the other hand, tri- and tetracationic compounds were not affected by the diffusion potential because of their much lower lipophilicity. The membrane surface potential affected to the transport of polycationic compounds, similar to monocationic compounds. Therefore it appears that the membrane surface potential plays a common role in the transport of mono- and polycationic compounds across cell membranes. On the intestinal basolateral membrane, it was found that there was a Na+/putrescine symporter. This recognized dicationic compounds and transported them from the blood into intestinal cells. This transporter did not recognize spermine and spermidine. Furthermore, we found a novel transport system, a Na+/spermine antiporter, on the rat renal brush-border membrane. This transporter recognized aliphatic polycation, which has more than four amino groups, and actively secreted spermine and trientine into the renal proximal tubules in vitro and in vivo. However, this transporter did not recognize trientine-copper complex. These results are useful for the prediction of the intestinal absorption and renal excretion of polyamine derivatives.

The Transport Mechanism of Polycationic Compounds across Intestinal and Renal Cell Membrane