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-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 (Kt) of 8 microM. 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.
Lazaruk
K D
KD
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85724.
Wright
S H
SH
D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002412:Cations; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008871:Microvilli / Q000378:metabolism; D009994:Osmolar Concentration; D011817:Rabbits; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism*; D013997:Time Factors
D002412:Cations; D007477:Ions; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D006859:Hydrogen; D015655:1-Methyl-4-phenylpyridinium