Substrate and inhibitor specificity of anion exchangers on the brush border membrane of rabbit ileum.

Abstract

In previous studies we have found that several anions can be transported by an exchange process in rabbit ileal brush border membranes. We demonstrated exchanges of C1 for OH or HCO3, SO4 for OH, oxalate for OH, and oxalate for C1. The purpose of these studies was to determine the number of distinct carriers mediating these exchanges. We utilized substrate and inhibitor specificity studies to distinguish between different anion exchange transporters. We conclude that SO4:OH and oxalate:OH exchange occur on the same carrier because: (i) pH-gradient stimulated transport of both 14C-oxalate and 35SO4 were equally sensitive to cis-inhibition by unlabeled SO4 or oxalate; and (ii) both were inhibited equally by K. We conclude that oxalate:OH and oxalate:C1 exchanges occur on different carriers because: (i) C1 or SO4 caused unequal cis-inhibition of these two exchanges; and (ii) as compared to oxalate:C1 exchange, oxalate:OH exchange was more sensitive to inhibition by probenecid and K and less sensitive to inhibition by bumetanide. Finally, we conclude that oxalate:C1 exchange and C1:HCO3 exchange occur on different carriers because: (i) C1:HCO3 exchange was almost completely insensitive to cis-inhibition by oxalate; and (ii) oxalate:C1 exchange was more sensitive to inhibition by DIDS and bumetanide than C1:HCO3 exchange. Thus we have found that there are at least three separate anion exchangers on rabbit ileal brush border: a Cl:HCO3 exchanger; a SO4:OH exchanger, which also transports oxalate; and an oxalate:C1 exchanger.