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

Katherine D Aver Lazaruk, Stephen Wright

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Abstract

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 (Kt) 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 languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume258
Issue number3 27-3
StatePublished - 1990

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Tetraethylammonium
Microvilli
Kidney
Membranes
Cations
1-Methyl-4-phenylpyridinium
Active Biological Transport
Neurotoxins
Rabbits

Keywords

  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 1-methyl-4-phenylpyridinium
  • Countertransport
  • Kidney
  • Organic cation
  • Rabbit
  • Tetraethylammonium

ASJC Scopus subject areas

  • Physiology

Cite this

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abstract = "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 (Kt) 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.",
keywords = "1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1-methyl-4-phenylpyridinium, Countertransport, Kidney, Organic cation, Rabbit, Tetraethylammonium",
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T1 - MPP+ is transported by the TEA+-H+ exchanger of renal brush-border membrane vesicles

AU - Lazaruk, Katherine D Aver

AU - Wright, Stephen

PY - 1990

Y1 - 1990

N2 - 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 (Kt) 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.

AB - 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 (Kt) 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.

KW - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

KW - 1-methyl-4-phenylpyridinium

KW - Countertransport

KW - Kidney

KW - Organic cation

KW - Rabbit

KW - Tetraethylammonium

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