Effect of DIDS on renal tubular transport

Abstract

Two stilbene derivates that had been used to covalently label the Cl- carrier in the erythrocyte were investigated for reactivity with the renal organic anion system. These compounds, 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) and (4,4'-diisothiocyano)-dihydrostilbene-2,2'-disulfonate (H2DIDS), were found to be potent inhibitors (Ki congruent to 35 microM) of p-aminohippurate (PAH) transport in the renal cortical slice without affecting tetraethylammonium (TEA) transport or tissue viability. During renal clearance studies performed in the perfused kidney, DIDS decreased the PAH/inulin clearance ratio to congruent to 1. When the possible renal transport of [3H]H2DIDS was investigated, the renal slice transport or binding of [3H]H2DIDS reached a slice-to-medium ratio of congruent to 6, and this accumulation was decreased by probenecid. In perfused kidney experiments, the [3H]H2DIDS/inulin clearance ratio was congruent to 0.8. Since probenecid reduced this clearance ratio to congruent to 0.5, there was the possibility that H2DIDS underwent tubular secretion. In conclusion, DIDS and H2DIDS interacted with the renal organic anion transport system, which indicated that these compounds were possible probes for this transport system.

Aortic responses to vanadate: independence from (Na,K)-ATPase and comparison of Dahl salt-sensitive and salt-resistant rats.

“…1 *' 13 We found that 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS) at 10"' M completely blocked the aortic response to 10" 3 M vanadate but had no effect on contractions induced by 60 mM K + or 10"* M norepinephrine. Thus, it appears that the vanadate anion, VO; 3 , must be taken into smooth muscle cells by the anion transport system prior to causing contraction, although we have no direct studies of radioactive vanadate uptake in aortic smooth muscle cells.…”

Electrogenic sodium/bicarbonate cotransport in rabbit renal cortical basolateral membrane vesicles.

“…The cortex of each kidney was sliced and homogenized with an Omni mixer (Dupont Instruments, Newton, CT; setting 10; 4 min) in the same buffer. The resultant slurry was centrifuged for 15 min at 2,450 g. Supernatants were recentrifuged at 35,000 g for 30 min. The fluffy layer of the pellet was suspended in 250 mM sucrose, 10 mM Hepes/Tris, pH 7.5, 1 mM magnesium chloride buffer, homogenized by passing through a 22-gauge needle and recentrifuged at 50,000 g for 30 min.…”

Indomethacin secretion in the isolated perfused proximal straight rabbit tubule. Evidence for two parallel transport mechanisms.

“…In theory, DIDS could simply be a competitive inhibitor of the anion transport system as was also suggested by Koshier et al (30). However, the fact that DIDS only minimally affected J, and the fact that DIDS could inhibit Jindo by at most 50%, makes this unlikely.…”

“…However, the fact that DIDS only minimally affected J, and the fact that DIDS could inhibit Jindo by at most 50%, makes this unlikely. It might be argued that albumin in the bathing solution may have blunted the effect of DIDS (15,16,30). This seems unlikely, since the final concentration of albumin in the bath (0.1%) was below that which reversed the inhibition of PAH transport caused by DIDS and SITS (15,30).…”

“…It might be argued that albumin in the bathing solution may have blunted the effect of DIDS (15,16,30). This seems unlikely, since the final concentration of albumin in the bath (0.1%) was below that which reversed the inhibition of PAH transport caused by DIDS and SITS (15,30). Furthermore, concentrations of DIDS were used an order of magnitude higher than those which caused maximal effects on indomethacin transport (Fig.…”