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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Coupling between proximal tubular transport processes. Studies with ouabain, SITS and HCO3-free solutions.

The rate of active transport by the proximal renal tubule of amino acid (L-histidine), sugar (alpha-methyl-D-glycoside), H+ ions (glycodiazine), phosphate and para-aminohippurate was evaluated by measuring the zero net flux concentration difference (deltac) of these substances. In the case of calcium the electrochemical potential difference (delta + zF-CIdeltaphi/RT) was the criterion employed. The rate of isotonic Na+-absorption (JNa) was measured with the shrinking droplet method. The effect of ouabain on the transport of these substances was tested in the golden hamster and the effect of SITS (4-acetamido-4'isothiocyanatostilbene 2,2'-disulfonic acid) was observed in rats. Ouabain (1 mM) applied peritubularly incompletely inhibited JNa (80%), but in combination with acetazolamide (0.2 mM) the inhibition was almost complete (93%). In addition, ouabain inhibited the sodium coupled (secondary active) transport processes of L-histidine, alpha-methyl-D-glycoside, calcium and phosphate by more than 75%. It did not affect H+ (glycodiazine) transport and PAH transport was only slightly affected. When SITS (1 mM) was applied from both sides of the cell it inhibited H+ (glycodiazine) transport by 72% and reduced JNa by 38% when given from only the peritubular cell side. SITS (1 MM), however, had no significant affect on H+ secretion and sodium reabsorption if it was applied from only the luminal side. Furthermore it had no affect on the other transport processes tested, regardless of the cell side to which it was applied. When the HCO-3 buffer or physically related buffers were omitted from the perfusate the absorption of Na+ was reduced by 66%, phosphate by 44%, and L-histidine by 15%. All the other transport processes tested were not significantly affected. The data are consistent with the hypothesis that the active transport processes of histidine, alpha-methyl-D-glycoside and phosphate, which are located in the brush border, are driven by a sodium gradient which is abolished by ouabain. This may also apply to the Na+-Ca2+ countertransport located at the contraluminal cell side. The residual Na+ transport remaining in the presence of ouabain is likely to be passively driven by the continuing H+ transport which probably is driven directly by ATP. SITS seems to inhibit the exit step of HCO-3 from the cell and secondary to that, the luminal H+-Na+ exchange and consequently the Na+ reabsorption. In the absence of HCO-3 buffer in the perfusates the luminal H+-Na+ exchange seems to be affected and the pattern of inhibition of the other transport processes is almost the same as with SITS. The different effects on Pi reabsorption observed under these conditions might be explained by possible variations in intracellular pH.[1]


  1. Coupling between proximal tubular transport processes. Studies with ouabain, SITS and HCO3-free solutions. Ullrich, K.J., Capasso, G., Rumrich, G., Papavassiliou, F., Klöss, S. Pflugers Arch. (1977) [Pubmed]
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