Rabbit renal brush-border membrane vesicles (BBMV) were used to study the transport of the cationic neurotoxin, 1-methyl-4-phenylpyridinium (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.
|Original language||English (US)|
|Journal||American Journal of Physiology - Renal Fluid and Electrolyte Physiology|
|Issue number||3 27-3|
|State||Published - Jan 1 1990|
- 1-me thyl-4-phenyl-1,2,3,6-tetrahydropyridine
- organic cation
ASJC Scopus subject areas