Contraluminal sulfate transport in the proximal tubule of the rat kidney

Publisher Website
Google Scholar
Abstract
In order to study the specificity for the contraluminal sulfate transport system the inhibitory potency of disulfonates, di-, tricarboxylates and sulfocarboxylates on the35SO 4 2− influx from the interstitium into cortical tubular cells in situ has been determined. The following was found: 1) Methane- and ethane-disulfonate as well as benzene-1,3-disulfonate inhibit contraluminal35SO 4 2− influx (with an (app.Ki of 2− or OH-group in position 4. However, OH-groups at position 4 and 5 or 4 and 6 abolish the inhibitory potency. 3) The naphthalene disulfonates tested inhibit only if they have an OH-group in ortho-position to one SO3H group. 4) The stilbene disulfonates H2DIDS and DNDS inhibit the contraluminal35SO 4 2− influx with high (app.Ki≈0.8 mmol/l), DADS with lower potency (app.Ki≈6 mmol/l). 5) Amongst the tested aliphatic di- and tricarboxylates inhibition was exerted by oxalate (app.Ki 1.1 mmol/l) and maleate (app.Ki 3.8 mmol/l), but not by malonate, hydroxymalonate and citrate. 6) Out of the tested benzenedicarboxylates only those inhibit which have the COO−-groups directly on the ring in 1,2 and 1,3 position (app.Ki 4.0 and 2.7 mmol/l), but not in the 1,4 position. An additional OH-group in position 4 augments the inhibitory potency of 1,3 benzene-dicarboxylates (app.Ki 0.8 mmol/l), while an OH group on position 5 abolishes it. 7) The benzene tricarboxylates (BTC) inhibit in the sequence 1,2,3-BTC>1,3,5-BTC>1,2,4-BTC (app.Ki 0.9, 1.5 and 4.2 mmol/l, respectively). 8) The carboxy-benzene-sulfonates inhibit also in the 1,2 and 1,3 position only (app.Ki 6.7 and 5 mmol/l), but not in the 1,4 position. Addition of an −OH-group to the 3-carboxy-1-benzene-sulfonate forming 4-hydroxy-3-carboxy-1-benzene-sulfate augments the inhibitory potency drastically (app.Ki 0.32 mmol/l), while a NH2 substitution at the same position leaves it unchanged (app.Ki 4.7 mmol/l). If, however, ethylamine instead of NH2 is used as substituent, the inhibitory potency is almost as high as of 4-hydroxy-3-carboxy-1-benzene-sulfonate (app.Ki≈0.6 mmol/l). Amongst the dicarboxy-benzene-sulfonates, 3,4-carboxy-benzene-1-sulfonate inhibits (app.Ki ca. 2 mmol/l), while 3,5-carboxy-benzene-1-sulfonate does not. The data indicate that a strong interaction of substrate with the sulfate transporter is given, when two charged groups (COO− and/or SO 3 − ) are present in a distance equivalent to the meta-position on the benzene ring and an additional hydrogen bond forming OH- or −NH-group. Hydrogen bond forming groups and charged groups in other positions usually abolish the inhibitory potency.