Inhibition of H,K‐ATPase and Na,K‐ATPase by DIDS, a disulphonic stilbene derivative

• Published in: Acta physiologica Scandinavica 1988-12, Vol.134 (4), p.543-547
• Main Authors: VEGA, F. V., CABERO, J. L., MÅRDH, S.
• Format: Article
• Language: English
• Subjects: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid - analogs & derivatives; 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid - pharmacology; Adenosine Triphosphatases - metabolism; adenosinetriphosphatase; Animals; Biological and medical sciences; Cell Membrane - metabolism; DIDS; disulphonic stilbenes; Fundamental and applied biological sciences. Psychology; Gastric Mucosa - enzymology; gastric vesicles; H(+)-K(+)-Exchanging ATPase; H,K‐ATPase; Kidney - enzymology; Na,K‐ATPase; Potassium Chloride - metabolism; proton transport inhibitors; Protons; Sodium-Potassium-Exchanging ATPase - metabolism; Stilbenes - pharmacology; Stomach; Swine; Vertebrates: digestive system
• ISSN: 0001-6772; 1365-201X
• DOI: 10.1111/j.1365-201X.1988.tb10633.x

Disulphonic stilbenes are effective inhibitors of an anion exchanger which is present in the plasma membranes of many cells (Cabantchik et al. 1978). In the present study, the effects of 4,4′‐diisothiocyano‐2,2′‐disulphonic stilbene acid (DIDS) on the transport activity of the hydrochloric acid pump isolated from pig stomach (H,K‐ATPase, EC 3.6.1.36) were tested. Half‐maximal inhibition of proton transport carried out by the H,K‐ATPase in the isolated vesicles was observed at micromolar concentrations of DIDS. The effects of DIDS on the adenosine‐triphosphatase and p‐nitrophenyl‐phosphatase activities of isolated H,K‐ATPase were also studied and compared with those of the kinetically and structurally related Na,K‐ATPase (EC 3.6.1.37). Half‐maximal inhibition of the enzymatic activities of both enzymes were observed in the micromolar range of DIDS. The lipid bilayer of the gastric vesicle membrane is highly asymmetric and the original cytosolic side is facing the outside of the vesicle. Since DIDS does not readily cross the membrane, it is most likely that DIDS exerts its inhibitory effects by modifying the transport ATPases on their cytosolic sides.