RT-PCR-based evidence for the in vivo stimulation of renal tubular p-aminohippurate (PAH) transport by triiodothyronine (T3) or dexamethasone (DEXA) in kidney tissue of immature and adult rats

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2003, Vol.54 (5), p.367-373
• Main Authors: Bahn, Andrew, Hauss, Achim, Appenroth, Dorothea, Ebbinghaus, Diana, Hagos, Yohannes, Steinmetzer, Peter, Burckhardt, Gerhard, Fleck, Christian
• Format: Article
• Language: English
• Subjects: age; Biological and medical sciences; dexamethasone; Medical sciences; OAT1; p-aminohippurate; Pharmacology. Drug treatments; rat; renal cortical slices; Renal tubular transport; RT-PCR; stimulation; triiodothyronine; Urinary system
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1078/0940-2993-00272

Our previous studies have shown that a pre-treatment of rats with triiodothyronine (T3) or dexamethasone (DEXA) increases renal PAH excretion significantly. This stimulation was accompanied by an enhanced protein synthesis within the renal cortex. To explore the molecular basis for this sub-chronic induction process, we investigated the stimulation of PAH accumulation in renal cortical slices as well as the expression level of organic anion transporter 1 (OAT1), the recently cloned renal basolateral PAH-transporter, using RT-PCR techniques under the applied conditions. 10- and 55-day-old Han:WIST rats were treated in vivo with T3 (20 μg/100 g b.wt.) or DEXA (60 μg/100 g b.wt.), both for 3 days, once daily. Renal cortical slices were incubated for 2 hours in Cross-Taggart medium and PAH uptake into kidney tissue was measured time dependently (slice to medium ratio, Q S/M). The accumulation capacity is comparable between immature and mature rats (control-Q S/M: 6.7 ± 0.1 vs. 6.9 ± 0.2, respectively). Both age groups showed a significant increase of PAH accumulation capacity after T3 treatment (10-day-old rats: 15.0 ± 0.2; 55-day-old rats: 11.7 ± 1.3). After DEXA pre-treatment, PAH accumulation was only slightly changed (10-day-old rats: 5.9 ± 0.2; 55-day-old rats: 8.2 ± 1.3). Semi-quantitative measurements of OAT1 mRNA expression level showed a significant increase of OAT1 mRNA after pre-treatment with both T3 and DEXA in the two age groups. Thus, this is the first evidence that T3 and DEXA pre-treatment induces the expression of OAT1.