Contraluminal sulfate transport in the proximal tubule of the rat kidney

Abstract

In order to study the specificity of the contraluminal sulfate transport system the inhibitory potency of salicylate analogs (5 mmol/l each) on the³⁵SO ₄ ²⁻ influx from the interstitium into cortical tubular cells in situ has been determined. The following was found: 2-hydroxybenzoate (salicylate), per se, did not inhibit contraluminal³⁵SO ₄ ²⁻ influx. The same holds when an additional NH₂-group was introduced in position 4 or 5, or when an additional Cl-group was introduced in position 4. When an additional Cl- or NO₂-group was introduced in position 5 a moderate inhibition was seen (app.K_i≈4 mmol/l). However, introduction of 2 Cl- or 2 NO₂-groups in position 3 and 5 creates compounds with strong inhibitory potency (app.K_i≈0.5 mmol/l). 2-hydroxy-3,5-iodobenzoate inhibited too, but with a smaller inhibitory potency (app.K_i≈2.3 mmol/l). 2-hydroxybenzoate analogs, which have a carboxy- or sulfo-group in position 5, exerted strong inhibition, those with a acetyl- or butyryl-group exerted moderate inhibition. 1-Naphthol-2-carboxylate did not inhibit, while 1-naphthol-4-sulfamoyl-2-carboxylate did. Amongst the dihydroxybenzoates, 2,3- and 2,5-dihydroxybenzoate did not inhibit contraluminal³⁵SO ₄ ²⁻ influx, while 2,4- and 2,6-dihydroxybenzoate did. The data indicate that a hydroxy-group in ortho-position and an electro-negative group in the meta-position to the carboxyl group and paraposition to the hydroxy-group are essential for interaction with the contraluminal sulfate transport system. The ability of 2,6-dihydroxybenzoate to inhibit might be explained by its ability to undergo mesomeric conformation.