MPP⁺ is transported by the TEA⁺-H⁺ exchanger of renal brush-border membrane vesicles

Rabbit renal brush-border membrane vesicles (BBMV) were used to study the transport of the cationic neurotoxin, 1-methyl-4-phenyl-pyridinium (MPP⁺). An outwardly directed H⁺-gradient stimulated MPP⁺ uptake and led to the development of an active accumulation of MPP⁺ within the vesicles. H⁺-gradient driven MPP⁺ transport was saturable, with a maximal transport rate of 3 nmol · mg^-1 ± min^-1 and an apparent Michaelis constant (K_t) of 8 μM. MPP⁺ and tetraethylammonium (TEA) behaved as competitive inhibitors of one another's transport in renal BBMV, suggesting the presence of a common transport pathway for these organic cations. At an ambient pH of 7.5, preloading BBMV with MPP⁺ failed to stimulate TEA uptake, although trans TEA did stimulate MPP⁺ uptake. Increasing ambient pH to 8.5 (i.e., reducing competition between H⁺ and these organic cations for a common transport pathway) led to a clear reciprocal trans stimulation of TEA and MPP⁺ fluxes. With an equilibrium-shift protocol, a trans concentration of MPP⁺ energized uphill transport of TEA. We conclude that MPP⁺ and TEA share a common organic cation-H⁺ exchange pathway in the renal brush border, although turnover of an MPP⁺-loaded exchanger is slow compared with that for a TEA or H⁺-loaded exchanger.