Mechanism of ochratoxin A transport in kidney.
The effect of the fungal metabolite (mycotoxin) Ochratoxin A (OTA) on the transport of p-amino[3H]hippurate (PAH), a prototypic organic anion, was examined in renal brush border (BBMV) and basolateral membrane vesicles (BLMV). OTA was as effective an inhibitor of PAH uptake in both membranes as probenecid. The dose response curves for OTA in BBMV and BLMV gave IC50 values of 20 +/- 6 and 32 +/- 7 microM, respectively. The effect was specific since the transport of the organic cation N1-methylnicotinamide was not affected. The phenomenon of counterflow was studied to establish that OTA is translocated. OTA produced trans stimulation of PAH transport in both BBMV and BLMV, demonstrating that OTA is transported across both these membranes. The data suggest that OTA interacts with the PAH transport system in both BBMV and BLMV. We conclude that OTA transport in the kidney is mediated via the renal organic anion transport system.
Sokol
P P
PP
Department of Pharmacology, State University of New York, Syracuse.
Ripich
G
G
Holohan
P D
PD
Ross
C R
CR
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004285:Dogs; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D009793:Ochratoxins / Q000493:pharmacokinetics* / Q000494:pharmacology; D014316:Tritium; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D009793:Ochratoxins; D014316:Tritium; C025589:ochratoxin A; D009536:Niacinamide; C008472:N-methylnicotinamide; D010130:p-Aminohippuric Acid