ausblenden:
Schlagwörter:
Epithelial transport; Contraluminal cell membrane
Zusammenfassung:
In order to study the specificity for the contraluminal sulfate transport system the inhibitory potency of disulfonates, di-, tricarboxylates and sulfocarboxylates on the 35SO2−4 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 contraluminal 35SO2−4 influx (with an (app. Ki of <6 mmol/l), while benzene-1,2- and 1,4-disulfonate do not. 2) The inhibitory potency of 1,3-benzene disulfonate is slightly augmented by an additional NH2 − 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 contraluminal 35SO2−4 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.
