Cadmium inhibition of basolateral solute fluxes in rabbit renal tubules and the nature of cycloleucine uptake.
The objective of this investigation was to determine whether Cd inhibition of amino acid transport across basolateral (BL) cell membranes in renal tubules results from a direct toxic action at that site. The concentration ratio (R) of cycloleucine in cell water/arterial plasma at steady state in nonfiltering rabbit kidneys consistently exceeded 1.0, thus confirming the active nature of BL amino acid uptake. BL cycloleucine extrusion, though down the concentration gradient, has previously been shown to be greatly slowed in Cd-poisoned animals; nevertheless, R remained unchanged. Active uptake and passive extrusion of cycloleucine must therefore be equally sensitive to Cd, a fact strongly suggesting an indirect action of the metal on BL solute transfer. This hypothesis is strengthened by the observation that R for paraaminohippurate (PAH), another solute actively accumulated across BL membranes, also remained unaffected by Cd poisoning. The reduction in R(PAH) by the direct transport inhibitor probenecid served as positive control. The additional finding that R(cycloleucine) is also depressed by probenecid, as well as by excess PAH, indicates some overlap in substrate specificities of the two carrier systems. The systems are not identical, however, as can be deduced from the observation that L-leucine affected only transport of cycloleucine, not that of PAH.
Foulkes
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Department of Environmental Health, University of Cincinnati College of Medicine, Ohio 45267-0056.
Blanck
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D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D003515:Cycloleucine / Q000493:pharmacokinetics* / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D007930:Leucine / Q000494:pharmacology; D008297:Male; D011339:Probenecid / Q000494:pharmacology; D011817:Rabbits; D010130:p-Aminohippuric Acid / Q000378:metabolism / Q000494:pharmacology
D002104:Cadmium; D003515:Cycloleucine; D007930:Leucine; D011339:Probenecid; D010130:p-Aminohippuric Acid