Effects of Two Inhibitors of Anion Transport on Bone Resorption in Organ Culture*

The present investigation was undertaken to examine the effects of 4-acetamido-4'-isothiocyanostilbene-2,2-disulfonic acid (SITS) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), known amino-reactive and selective inhibitors of anion exchange across the plasma membrane, on bone resorption in organ cultures of fetal rat long bones. Cultures were treated with SITS and DIDS under control unstimulated conditions or with PTH. Both SITS and DIDS were found to be potent inhibitors of 45Ca release from previously labeled fetal rat long bones. Both control resorption and the response to PTH were inhibited in a dose-related fashion. SITS and DIDS also inhibited the incorporation of [3H]thymidine in bone. The effects on resorption and [3H]thymidine incorporation were reversible when the drugs were withdrawn. These findings indicate that SITS and DIDS are potent inhibitors of bone resorption which may act by blocking the anion exchange, Cl-/HCO3-.