Contraluminal sulfate transport in the proximal tubule of the rat kidney. IV. Specificity: salicylate analogs.

In order to study the specificity of the contraluminal sulfate transport system the inhibitory potency of salicylate analogs (5 mmol/l each) on the 35SO4(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 contraluminal 35SO4(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. Ki approximately equal to 4 mmol/l). However, introduction of 2 Cl- or 2NO2-groups in position 3 and 5 creates compounds with strong inhibitory potency (app. Ki approximately equal to 0.5 mmol/l). 2-hydroxy-3,5-iodobenzoate inhibited too, but with a smaller inhibitory potency (app. Ki approximately equal to 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 contraluminal 35SO4(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.