Multiple transport systems for organic cations in renal brush-border membrane vesicles

Abstract

The characteristics of guanidine uptake in brush-border membrane vesicles isolated from rabbit renal cortex were investigated. Guanidine uptake was markedly stimulated by an outwardly directed H+ gradient, resulting in a transient uphill transport. This stimulation was not due to an inside-negative, H+-diffusion potential because an ionophore-induced H+-diffusion potential and a K+-diffusion potential (both inside-negative) failed to enhance guanidine uptake. The H+ gradient itself appeared to be the driving force for the uptake. These data suggest that guanidine-H+ antiport (or guanidine-OH- symport) is the mechanism of guanidine uptake in these membrane vesicles. Guanidine uptake was only minimally inhibited by organic cations such as tetraethylammonium, N1-methylnicotinamide, and choline, but many other organic cations such as amiloride, clonidine, imipramine, and harmaline caused considerable inhibition. Uptake of radiolabeled guanidine was inhibited more effectively by guanidine than by tetraethylammonium, whereas uptake of radiolabeled tetraethylammonium was inhibited more effectively by tetraethylammonium than by guanidine. beta-Lactam antibiotics did not inhibit guanidine uptake but did inhibit tetraethylammonium uptake. Kinetic analysis showed that there were at least two kinetically distinct carrier systems for guanidine uptake, whereas tetraethylammonium uptake occurred via a single carrier system. These data provide evidence that renal brush-border membranes possess multiple carrier systems for organic cations.