Peritubular transport of ochratoxin A in rabbit renal proximal tubules.
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 Jmax value of 0.12 +/- 0.4 nmol/mg of protein/min and a Km value of 1.4 +/- 0.1 microM. The apparent Michaelis constants for inhibition of [3H]para-aminohippurate (PAH) uptake by ochratoxin A inhibition was 1.5 microM, which is similar to the Km 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 approximately 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 Ki 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 microM, 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.
Groves
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CE
Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, USA.
Morales
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M
Wright
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D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002210:Caprylates / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D009183:Mycotoxins / Q000493:pharmacokinetics*; D009793:Ochratoxins / Q000493:pharmacokinetics*; D010894:Piroxicam / Q000494:pharmacology; D011817:Rabbits; D013535:Suspensions; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D002210:Caprylates; D009183:Mycotoxins; D009793:Ochratoxins; D013535:Suspensions; D010894:Piroxicam; C025589:ochratoxin A; C031492:octanoic acid; D010130:p-Aminohippuric Acid