Renal Excretion and Tubular Transport of Organic Anions and Cations

Roch-Ramel, F; Besseghir, Kamel; Murer, Heini

doi:10.1002/cphy.cp080248

Cited by 32 publications

(36 citation statements)

References 410 publications

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“…Transport of para-aminohippurate (PAH) is a prototype of organic anion secretion in the proximal renal tubule [19,21,23,35]. Its contraluminal uptake step, i.e.…”

Section: Introductionmentioning

confidence: 99%

Luminal transport step of para -aminohippurate (PAH): transport from PAH-loaded proximal tubular cells into the tubular lumen of the rat kidney in vivo

Ullrich

Rumrich

1997

Pfl�gers Archiv European Journal of Physiology

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Proximal tubular cells were loaded for 10 s with [3H]para-aminohippurate ([3H]PAH) by microperfusing the peritubular capillaries with Ringer solution containing 0.05 mmol/l PAH. Immediately thereafter [3H]PAH influx from cells into a column of equilibrium solution injected into the oil-filled tubular lumen was measured by re-aspirating the fluid after 1-10 s of contact time. The rise of luminal PAH concentration within 2 s of contact time was almost linear, reaching a luminal/capillary concentration ratio of 1.6 after 2 s and of 3.2 after 5 s. The 2-s PAH concentration ratio was not changed when different manoeuvres were applied to depolarize proximal tubular cells. Also, the 2-s PAH concentration ratio was not influenced by varying the luminal pH from 6.0 to 8.0 or the luminal Cl- concentration from zero to 134 mmol/l or when either 5 mmol/l urate or 25 mmol/l lactate was in the luminal perfusate. A decrease in the 2-s PAH concentration ratio, i.e. trans-inhibition, was observed when 25 or 50 mmol/l HCO3- (-50%) was in the luminal perfusate. Trans-inhibition was also seen with 5 mmol/l of the following substituted benzoates: 2-hydroxy-benzoate (-58%), 2-methoxy-benzoate (-46%), 2-hydroxy-benzoate-acetyl ester (-36%), 2-hydroxy-3,5-dinitro-benzoate (-48%), 3,5-dichloro-benzoate (-49%), and 2,3,5-trichloro-benzoate (-45%). No effect was seen with benzoate, 3-hydroxy-benzoate, 2-chloro-benzoate, 2-nitro-benzoate, 2,5-dinitro-benzoate, 3-sulfamoyl-benzoate and 4-sulfamoyl-benzoate. However, analogues of the latter two compounds possessing two additional side groups, such as furosemide and piretanide, or a hydrophobic moiety, such as probenecid, were inhibitory (by -62, -41 and -49% respectively). Phenoxyacetate had no effect; however, it inhibited if in addition it had three chloro groups, as in 2,4,5-trichlorophenoxyacetate (-71%) or a hydrophobic carbamoyl side group, as in mersalylic acid (salyrgan, -75%). Benzene-sulfonate trans-inhibited (-33%), as did phenolsulfonphthalein (phenol red, -39%) and sulfofluorescein (-55%). However, the trans-inhibitory effect of the corresponding carboxy-compounds was absent (phenolphthalein) or weaker (fluorescein, -42%). The trans-inhibitory effect of the uricosurics ethacrynic acid (-53%), tienilic acid (-55%) indacrinone (-72%) and benzbromarone (-42%) could be attributed to two chloro or bromo side groups on the benzene ring. Other trans-inhibiting uricosuric substances were indomethacin (-42%), sulfinpyrazone (-38%), losartan (-80%) its metabolite EXP 3174 (-55%), and AA 193 (-65%). These organic acids, with pKa values between 2.8 and 4.9, possess chloro and sulfin groups, as well as heterocyclic 5-ring and hydrophobic ring or chain areas. No significant effect was seen with 5 mmol/l PAH, 2-oxo-glutarate, DIDS, cGMP, prostaglandin E2, cortisol, benzylamiloride, pyrazinoic acid and 25 mmol/l lactate. Our data indicate that in situ the secretory luminal PAH transport proceeds in a non-rheogenic fashion, per exclusionem by anion exchange. The observed trans-inhibition of PAH s...

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“…Transport of para-aminohippurate (PAH) is a prototype of organic anion secretion in the proximal renal tubule [19,21,23,35]. Its contraluminal uptake step, i.e.…”

Section: Introductionmentioning

confidence: 99%

Luminal transport step of para -aminohippurate (PAH): transport from PAH-loaded proximal tubular cells into the tubular lumen of the rat kidney in vivo

Ullrich

Rumrich

1997

Pfl�gers Archiv European Journal of Physiology

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“…rOCT1 is the first member of a new, rapidly growing protein family (2, 4 -10) that belongs to a major superfamily of transmembrane facilitators (12). The OCT family includes a second subtype, OCT2 (2,9), and the polyspecific renal anion transporter OAT1, which is known as the paraaminohippurate transporter (10,11,13). rOCT1 probably mediates the first step in the excretion of many organic cations in the kidney, small intestine, and liver, since it was localized in the basolateral membrane of renal proximal tubules and intestinal enterocytes and in the sinusoidal membrane of hepatocytes (14).…”

mentioning

confidence: 99%

A Reevaluation of Substrate Specificity of the Rat Cation Transporter rOCT1

Nagel¹,

Volk²,

Friedrich³

et al. 1997

Journal of Biological Chemistry

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The substrate specificity of the previously cloned rat cation transporter rOCT1, which is expressed in kidney, liver, and small intestine, was reevaluated. rOCT1 is the first member of a new protein family comprising electrogenic and polyspecific cation transporters that transport hydrophilic cations like tetraethylammonium, choline, and monoamine neurotransmitters. Previous electrical measurements suggested that cations like quinine, quinidine, and cyanine 863, which have been classified as type 2 cations in the liver, are also transported by rOCT1, since they may induce inward currents in rOCT1 expressing Xenopus oocytes (Busch, A. E., Quester, S., Ulzheimer, J. C., Waldegger, S., Gorboulev, V., Arndt, P., Lang, F., and Koepsell, H. (1996) J. Biol. Chem. 271, 32599 -32604). Tracer flux measurements with oocytes and with stably transfected human embryonic kidney cells showed that [3 H]quinine and [ 3 H]quinidine are not transported by rOCT1. The voltage dependence observed for the quinine-or quinidineinduced inward currents in rOCT1-expressing oocytes, and tracer efflux measurements indicate that the inward currents by type 2 cations are generated by the inhibition of electrogenic efflux of transported type 1 cations. Therefore, rOCT1 cannot contribute to transport of type 2 cations in the liver and the hepatic transporter for type 2 cations remains to be identified.

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“…Indeed, it is frequently assumed that interac tion of a molecule with the basolateral OC transporter simply requires that the com pound possesses a net positive charge [see 21,24], It is significant, therefore, that Ullrich and Rumrich [25] have found that interaction of the transporter with organic bases does not display a pH sensitivity consistent with the binding of substrate being limited to the protonated species. This led to his suggestion that the OC transporter senses the substrate's di pole structure and/or its ability to form hydro gen bonds, rather than the degree of ioniza tion.…”

Section: Specificity O F Basolateral Oc Transportmentioning

confidence: 99%

Characterization of Renal Brush-Border and Basolateral Membrane Transporters for Organic Cations

Wright¹

1996

Cell Physiol Biochem

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The renal proximal tubule is the site of active secretion of a diverse array of organic cations and bases (collectively, OCs). The basolateral entry step in transtubule OC transport involves an electrogenic facilitated diffusion process. OC exit into the tubule lumen is the active step in secretion and involves the carrier-mediated exchange of OC for H⁺. The specificity of these two processes is influenced less by steric characteristics of substrates than by their chemical lipophilicity, with both transporters displaying an increasing affinity for OCs of increasing lipophilicity. Several additional OC transporters exist within each membrane and the concerted activity of these processes permits the proximal tubule to effect the secretion of most OCs, and the selective reabsorption of others, and provides the tubule with a degree of ‘redundancy’ in the means available for secreting potentially toxic xenobiotic compounds from the body.

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Renal Excretion and Tubular Transport of Organic Anions and Cations

Abstract: The sections in this article are: Organic Anions Introduction Renal Excretion and Tubular Transport of Organic Anions Mechanisms Involved in Tubular Transport of Organic Anions Conclusions on the Renal Transport of Organic Anions Organic Cations Introduction … Show more

Cited by 32 publications

References 410 publications

Luminal transport step of para -aminohippurate (PAH): transport from PAH-loaded proximal tubular cells into the tubular lumen of the rat kidney in vivo

Luminal transport step of para -aminohippurate (PAH): transport from PAH-loaded proximal tubular cells into the tubular lumen of the rat kidney in vivo

A Reevaluation of Substrate Specificity of the Rat Cation Transporter rOCT1

Characterization of Renal Brush-Border and Basolateral Membrane Transporters for Organic Cations

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