In vitro stimulation of renal tubular p-aminohippurate transport by dexamethasone in rat kidneys and in intact kidney tissue of patients suffering from renal cell carcinoma.
The aim of this study was to test whether or not the accumulation of p-aminohippurate (PAH) can be increased in intact human renal cortical slices obtained from tumor-bearing kidneys of patients suffering from renal cell carcinoma (RCC). Tissue slices were incubated for 24 h in Williams medium E containing 0.01-50 microM dexamethasone. Thereafter slices were placed in PAH-containing Cross-Taggart medium and PAH uptake into kidney tissue was measured for 2 h. In both rat and human renal tissue slices, PAH uptake capacity increased significantly in a concentration-dependent manner after 24 h of incubation in dexamethasone-containing medium (rat, 136%; man, 156%). The stimulatory effect was already significant after 12 h of incubation. In additional experiments it was shown that incubation in triiodothyronine (T3)-containing medium has different effects: in man, T3 does not influence the PAH accumulation capacity of renal cortical slices whereas in rats PAH accumulation is significantly lower after 24 h of incubation with T3. Thus stimulation of tubular transport capacity can be performed in vitro in human renal cortical slices. Discrepancies between the effects of dexamethasone and T3 indicate different modes of action of the two hormones at the cellular level.
Fleck
C
C
Klinikum der Friedrich-Schiller-Universität Jena, Institut für Pharmacologie und Toxicologie, Germany. CFLE@mti-n.uni-jena.de
Kratochwil
E
E
Winterstein
K
K
Göckeritz
S
S
Schubert
J
J
D000368:Aged; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000494:pharmacology; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics*
D014284:Triiodothyronine; D003907:Dexamethasone; D010130:p-Aminohippuric Acid