LYSOSOMAL SULFATE TRANSPORT - INHIBITOR STUDIES

Sulfate derived from the degradation of macromolecules is released fro m lysosomes via a carrier mediated process. In order to further charac terize this process, recognized inhibitors of the erythrocyte band 3 a nion transporter were examined for their effects on the lysosomal syst em. Studies with band 3 transport site inhibitors such as DIDS, SITS a nd phenylglyoxal indicated that, similar to the case for the band 3 pr otein, the lysosomal transporter has critical lysine and arginine resi dues. Band 3 translocation pathway or channel blocking inhibitors had mixed effects on the lysosomal system. 1,2-Cyclohexanedione, which cov alently modifies a band 3 arginine residue distinct from that modified by phenylglyoxal, inhibited lysosomal sulfate transport. In contrast, the potent band 3 inhibitor dipyridamole had no effect on lysosomal s ulfate transport indicating that there are some structural differences between the erythrocyte and lysosomal anion transporters. The band 3 translocation inhibitors niflumic acid and dinitrofluorobenzene were b oth effective inhibitors of the lysosomal system. Cupric ion inhibited sulfate transport while Ca2+, Co2+, Mg2+, Mn2+, and Zn2+ had no inhib itory effects. Exposure of intact lysosomes to trypsin largely ablated transport of sulfate. This information should be useful in efforts to further elucidate the structure and function of the lysosomal sulfate transporter.