Bisubstrates: substances that interact with both, renal contraluminal organic anion and organic cation transport systems

1993 ◽  
Vol 425 (3-4) ◽  
pp. 300-312 ◽  
Author(s):  
K. J. Ullrich ◽  
G. Rumrich ◽  
C. David ◽  
G. Fritzsch
1990 ◽  
Vol 258 (6) ◽  
pp. F1599-F1607 ◽  
Author(s):  
P. P. Sokol ◽  
T. D. McKinney

The transports of [3H]tetraethylammonium (TEA), [3H]procainamide (PCA), and N1-[3H]methylnicotinamide (NMN) were studied in rabbit renal basolateral membrane vesicles (BLMVs) by use of a rapid filtration assay. All three compounds exhibited a similar uptake profile into the BLMVs and reached equilibrium by 1 h. In the presence of valinomycin, a K+ ionophore and K+ gradients (in to out), an inside-negative potential difference (PD) was generated that stimulated the uptake of TEA, PCA, and NMN by 1.9-, 1.9-, and 2.1-fold, respectively. The effect of PD could be blocked by the organic cation transport inhibitor mepiperphenidol. An inside-negative PD was also generated by a pH gradient (inside acidic). An overshoot of TEA uptake was produced, which was blocked by a valinomycin voltage clamp. Counterflow studies revealed that 1 mM TEA was capable of trans-stimulating 50 microM [3H]TEA uptake and producing a peak overshoot of nearly three times the equilibrium value, which was not abolished in the presence of a valinomycin voltage clamp or a gramicidin pH clamp. When an inside-negative PD was imposed on 1 mM TEA-loaded BLMVs, the uptake of [3H]TEA was 33% less. In contrast, neither NMN nor PCA produced a trans-stimulation of [3H]NMN or [3H]PCA transport, respectively. In addition, the effect of several organic cations on the TEA-TEA exchange mechanism was studied. Mepiperphenidol, PCA, choline, cimetidine, and NMN all demonstrated cis inhibition (82, 81, 58, 51, and 20%, respectively). Arginine, a basic amino acid, and probenecid, an organic anion transport inhibitor, had no effect. Choline was capable of trans-stimulating TEA uptake.(ABSTRACT TRUNCATED AT 250 WORDS)


2002 ◽  
Vol 90 (4) ◽  
pp. 181-186 ◽  
Author(s):  
Brett Grover ◽  
Christopher Auberger ◽  
Rangaprasad Sarangarajan ◽  
William Cacini

1994 ◽  
Vol 266 (3) ◽  
pp. F450-F458 ◽  
Author(s):  
C. E. Groves ◽  
K. K. Evans ◽  
W. H. Dantzler ◽  
S. H. Wright

The physiological characteristics of peritubular organic cation transport were examined by measuring the transport of the organic cation tetraethylammonium (TEA) in rabbit renal proximal tubule suspensions and isolated nonperfused rabbit renal proximal tubules. Peritubular organic cation transport in both single S2 segments and suspensions of isolated renal proximal tubules was found to be a high-capacity, high-affinity, carrier-mediated process. For tubule suspensions, the maximal capacity of the carrier for TEA (Jmax) and the concentration of TEA at 1/2 Jmax (Kt) (1.49 +/- 0.21 nmol.min-1.mg dry wt-1 and 131 +/- 16 microM, respectively), did not differ significantly from those measured in single S2 segments (Jmax, 1.16 +/- 0.075 nmol.min-1.mg dry wt-1; Kt, 108 +/- 10 microM). In addition, the pattern of inhibition of peritubular TEA transport by long-chain n-tetraalkylammonium compounds (n = 1-5) was both qualitatively and quantitatively similar in single S2 segments and tubule suspensions, exhibiting an increase in inhibitory potency with increasing alkyl chain length. For example, in tubule suspensions, apparent Michaelis constants for inhibition of TEA uptake ranged from 1.3 mM for tetramethylammonium (TMA) to 0.8 microM for tetrapentylammonium (TPeA). To determine whether these compounds were substrates for the peritubular organic cation transporter, their effect on the efflux of [14C]TEA from tubule suspensions was examined. A concentration of 0.5 mM of the short-chain tetraalkyls TMA or TEA increased the efflux of [14C]TEA (i.e., trans-stimulated) from tubules in suspension. The longer-chain tetraalkyls tetrapropylammonium, tetrabutylammonium, and TPeA all decreased the efflux of [14C]TEA from tubules in suspension; TPeA completely blocked efflux.(ABSTRACT TRUNCATED AT 250 WORDS)


2004 ◽  
Vol 449 (5) ◽  
pp. 423-441 ◽  
Author(s):  
Giuliano Ciarimboli ◽  
Eberhard Schlatter

1998 ◽  
Vol 37 (2) ◽  
pp. 131-136 ◽  
Author(s):  
F. MARTEL ◽  
M.J. MARTINS ◽  
C. CALHAU ◽  
C. HIPÓLITO-REIS ◽  
I. AZEVEDO

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