Peritubular transport of ochratoxin A in rabbit renal proximal tubules

Carlotta E. Groves, Mark Morales, Stephen Wright

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The transport of the nephrotoxic mycotoxin ochratoxin A across the renal peritubular membrane was examined in suspensions of rabbit renal proximal tubules. Ochratoxin A transport across the peritubular membrane was a high- affinity, low-capacity carrier-mediated process with a J(max) value of 0.12 ± 0.4 nmol/mg of protein/min and a K(m) value of 1.4 ± 0.1 μM. The apparent Michaelis constants for inhibition of [3H]para-aminohippurate (PAH) uptake by ochratoxin A inhibition was 1.5 μM, which is similar to the K(m) value for ochratoxin A uptake in tubule suspensions and suggests that ochratoxin A could be a substrate for the organic anion pathway. The capacity and affinity for peritubular ochratoxin A transport were 40-fold lower and >100-fold greater, respectively, than those measured for the peritubular uptake of [3H]PAH in tubule suspensions. A concentration of 2.5 mM PAH, which reduced the uptake of [3H]PAH by 90%, reduced ochratoxin A uptake by only 40% to 50%, whereas probenecid concentrations of 0.6 to 2 mM reduced ochratoxin A accumulation in tubule suspensions up to ≃80% to 90%. This probenecid-sensitive, PAH-insensitive uptake of ochratoxin A suggested that at least one mediated pathway other than the organic anion transporter was involved in the peritubular uptake of this mycotoxin. A 2 mM concentration of the fatty acid octanoate and 1.5 mM concentration of the nonsteroidal anti- inflammatory agent piroxicam were as effective as probenecid in blocking ochratoxin A uptake. The apparent K(l) values for inhibition of ochratoxin A uptake by probenecid, piroxicam and octanoate were 30.5 ± 7.9, 23.2 ± 10.4 and 81.5 ± 8.7 μM, respectively. The ability of octanoic acid to inhibit ochratoxin A transport to the same extent as probenecid and a greater extent than PAH suggests that a separate fatty acid transport pathway may be involved in the accumulation of ochratoxin A by suspensions of rabbit renal proximal tubules.

Original languageEnglish (US)
Pages (from-to)943-948
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume284
Issue number3
StatePublished - Mar 1998

Fingerprint

Proximal Kidney Tubule
Rabbits
Probenecid
Suspensions
Piroxicam
Mycotoxins
ochratoxin A
Fatty Acids
Organic Anion Transporters
Membranes
Non-Steroidal Anti-Inflammatory Agents
Anions

ASJC Scopus subject areas

  • Pharmacology

Cite this

Peritubular transport of ochratoxin A in rabbit renal proximal tubules. / Groves, Carlotta E.; Morales, Mark; Wright, Stephen.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 284, No. 3, 03.1998, p. 943-948.

Research output: Contribution to journalArticle

@article{705b58a2c1aa43e8875c9620e31891d7,
title = "Peritubular transport of ochratoxin A in rabbit renal proximal tubules",
abstract = "The transport of the nephrotoxic mycotoxin ochratoxin A across the renal peritubular membrane was examined in suspensions of rabbit renal proximal tubules. Ochratoxin A transport across the peritubular membrane was a high- affinity, low-capacity carrier-mediated process with a J(max) value of 0.12 ± 0.4 nmol/mg of protein/min and a K(m) value of 1.4 ± 0.1 μM. The apparent Michaelis constants for inhibition of [3H]para-aminohippurate (PAH) uptake by ochratoxin A inhibition was 1.5 μM, which is similar to the K(m) value for ochratoxin A uptake in tubule suspensions and suggests that ochratoxin A could be a substrate for the organic anion pathway. The capacity and affinity for peritubular ochratoxin A transport were 40-fold lower and >100-fold greater, respectively, than those measured for the peritubular uptake of [3H]PAH in tubule suspensions. A concentration of 2.5 mM PAH, which reduced the uptake of [3H]PAH by 90{\%}, reduced ochratoxin A uptake by only 40{\%} to 50{\%}, whereas probenecid concentrations of 0.6 to 2 mM reduced ochratoxin A accumulation in tubule suspensions up to ≃80{\%} to 90{\%}. This probenecid-sensitive, PAH-insensitive uptake of ochratoxin A suggested that at least one mediated pathway other than the organic anion transporter was involved in the peritubular uptake of this mycotoxin. A 2 mM concentration of the fatty acid octanoate and 1.5 mM concentration of the nonsteroidal anti- inflammatory agent piroxicam were as effective as probenecid in blocking ochratoxin A uptake. The apparent K(l) values for inhibition of ochratoxin A uptake by probenecid, piroxicam and octanoate were 30.5 ± 7.9, 23.2 ± 10.4 and 81.5 ± 8.7 μM, respectively. The ability of octanoic acid to inhibit ochratoxin A transport to the same extent as probenecid and a greater extent than PAH suggests that a separate fatty acid transport pathway may be involved in the accumulation of ochratoxin A by suspensions of rabbit renal proximal tubules.",
author = "Groves, {Carlotta E.} and Mark Morales and Stephen Wright",
year = "1998",
month = "3",
language = "English (US)",
volume = "284",
pages = "943--948",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "3",

}

TY - JOUR

T1 - Peritubular transport of ochratoxin A in rabbit renal proximal tubules

AU - Groves, Carlotta E.

AU - Morales, Mark

AU - Wright, Stephen

PY - 1998/3

Y1 - 1998/3

N2 - The transport of the nephrotoxic mycotoxin ochratoxin A across the renal peritubular membrane was examined in suspensions of rabbit renal proximal tubules. Ochratoxin A transport across the peritubular membrane was a high- affinity, low-capacity carrier-mediated process with a J(max) value of 0.12 ± 0.4 nmol/mg of protein/min and a K(m) value of 1.4 ± 0.1 μM. The apparent Michaelis constants for inhibition of [3H]para-aminohippurate (PAH) uptake by ochratoxin A inhibition was 1.5 μM, which is similar to the K(m) value for ochratoxin A uptake in tubule suspensions and suggests that ochratoxin A could be a substrate for the organic anion pathway. The capacity and affinity for peritubular ochratoxin A transport were 40-fold lower and >100-fold greater, respectively, than those measured for the peritubular uptake of [3H]PAH in tubule suspensions. A concentration of 2.5 mM PAH, which reduced the uptake of [3H]PAH by 90%, reduced ochratoxin A uptake by only 40% to 50%, whereas probenecid concentrations of 0.6 to 2 mM reduced ochratoxin A accumulation in tubule suspensions up to ≃80% to 90%. This probenecid-sensitive, PAH-insensitive uptake of ochratoxin A suggested that at least one mediated pathway other than the organic anion transporter was involved in the peritubular uptake of this mycotoxin. A 2 mM concentration of the fatty acid octanoate and 1.5 mM concentration of the nonsteroidal anti- inflammatory agent piroxicam were as effective as probenecid in blocking ochratoxin A uptake. The apparent K(l) values for inhibition of ochratoxin A uptake by probenecid, piroxicam and octanoate were 30.5 ± 7.9, 23.2 ± 10.4 and 81.5 ± 8.7 μM, respectively. The ability of octanoic acid to inhibit ochratoxin A transport to the same extent as probenecid and a greater extent than PAH suggests that a separate fatty acid transport pathway may be involved in the accumulation of ochratoxin A by suspensions of rabbit renal proximal tubules.

AB - The transport of the nephrotoxic mycotoxin ochratoxin A across the renal peritubular membrane was examined in suspensions of rabbit renal proximal tubules. Ochratoxin A transport across the peritubular membrane was a high- affinity, low-capacity carrier-mediated process with a J(max) value of 0.12 ± 0.4 nmol/mg of protein/min and a K(m) value of 1.4 ± 0.1 μM. The apparent Michaelis constants for inhibition of [3H]para-aminohippurate (PAH) uptake by ochratoxin A inhibition was 1.5 μM, which is similar to the K(m) value for ochratoxin A uptake in tubule suspensions and suggests that ochratoxin A could be a substrate for the organic anion pathway. The capacity and affinity for peritubular ochratoxin A transport were 40-fold lower and >100-fold greater, respectively, than those measured for the peritubular uptake of [3H]PAH in tubule suspensions. A concentration of 2.5 mM PAH, which reduced the uptake of [3H]PAH by 90%, reduced ochratoxin A uptake by only 40% to 50%, whereas probenecid concentrations of 0.6 to 2 mM reduced ochratoxin A accumulation in tubule suspensions up to ≃80% to 90%. This probenecid-sensitive, PAH-insensitive uptake of ochratoxin A suggested that at least one mediated pathway other than the organic anion transporter was involved in the peritubular uptake of this mycotoxin. A 2 mM concentration of the fatty acid octanoate and 1.5 mM concentration of the nonsteroidal anti- inflammatory agent piroxicam were as effective as probenecid in blocking ochratoxin A uptake. The apparent K(l) values for inhibition of ochratoxin A uptake by probenecid, piroxicam and octanoate were 30.5 ± 7.9, 23.2 ± 10.4 and 81.5 ± 8.7 μM, respectively. The ability of octanoic acid to inhibit ochratoxin A transport to the same extent as probenecid and a greater extent than PAH suggests that a separate fatty acid transport pathway may be involved in the accumulation of ochratoxin A by suspensions of rabbit renal proximal tubules.

UR - http://www.scopus.com/inward/record.url?scp=0031935556&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031935556&partnerID=8YFLogxK

M3 - Article

VL - 284

SP - 943

EP - 948

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 3

ER -