Contraluminal sulfate transport in the proximal tubule of the rat kidney

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Abstract
In order to evaluate the specificity for the contraluminal sulfate transport system the inhibitory potency of phenol- and sulfonphthaleins, of sulfamoyl-compounds (diuretics) as well as diphenylamine-2-carboxylates (Cl− channel blockers) on the35SO 4 2− influx from the interstitium into cortical tubular cells in situ has been determined. The following was found: 1) Phenolsulfonphthalein (phenol-red) inhibited with an app.Ki-value of 1.7 mmol/l, while analogs which had additional Br-atoms in position 3 and/or 5, i.e. bromphenol-blue, bromcresol-purple and bromcresol-green, inhibited with an apparentKi of 0.1 and 0.5 mmol/l respectively. 2) Phenolphthalein and tetrabromphenolphthalein did not inhibit, while the disulfonate dyes bromsulfalein, fuchsin acid and indigocarmine inhibited with aKi between ≈1 and 3 mmol/l. The highest inhibitory potency in this class of compounds was seen with orange G (app.Ki 0.07 mmol/l). The monosulfonate dyes tested, fluoresceinsulfonate and orange I inhibited moderately with an app.Ki of ≈5 mmol/l. 3) The 3-sulfamoyl compounds inhibited to a varying degree, when they had a neighbouring −NH-group (furylmethylamino-group), i.e. in position 6 to the COOH or SO3H-group, or when they had a phenoxy-group in position 4. 4) 4-sulfamoylbenzoate and the related compounds probenecid, acetazolamide and hydrochlorothiazide inhibited with an app.Ki between 4 and 7 mmol/l. 5) All diphenylamine-2-carboxylate analogs inhibited with an app.Ki between 3 and 5 mmol/l, even when the −NH-group was replaced by an =O-group or the benzene ring was replaced by a pyrimidine ring, but not when it was replaced by a thiophen ring. In contrast, 4-phenylaminepyridine-3-sulfonate was ineffective, while diphenylamine-2-amino sulfonate exerted the highest inhibition of this group with an app.Ki of 1.4 mmol/l. When, however, the aminosulfonate group was replaced by a methylsulfonamide, the inhibitory potency disappeared. The data can be explained by inhibitory patterns found in previous papers for disulfonates [29], sulfonates with a hydrophobic moiety [28] or neighbouring OH-group [28, 29], carboxylates with a neighbouring −NH- or OH-group in position 2- and an electron-attracting group in position 5 [30].

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