Complex effects of papain on function and inhibitor sensitivity of the redcell anion exchanger AE1 suggest the presence of different transport subsites

Band 3 (AE1), the anion exchanger of the human erythrocyte membrane, mediat es not only fluxes of small hydrophilic anions (e.g., chloride, oxalate), b ut also the flip-flop of long-chain amphiphilic anions (e.g., dodecylsulfat e). Treatment of erythrocytes with papain, long known to inhibit the transp ort of the former type of anions, accelerates the transport of the latter t ype. In an attempt to elucidate the basis of these opposite responses to pa pain, several small amphiphilic arylalkyl sulfonates and -sulfates were tes ted for the response of their transport, via AE1, to papain. Although all t hese probes are most likely transported by a flux and not by flip-flop, the ir transport was inhibited by papain only in some cases, but accelerated in others. Different responses to papain therefore most likely do not reflect differences between transport by flux or by flip. The transports of different species of anions also differed considerably in the changes of their sensitivity, to noncovalent and some covalent inhibit ors, brought about by papain treatment. While oxalate transport remained as sensitive as in native cells, transports of small amphiphilic anions lost their sensitivity to a major extent, regardless of the inhibition or accele ration of their transport by papain. The results are discussed in the light of present concepts of the structura l organisation of AE1, and interpreted in terms of a model of different tra nsport subsites for different species of anions in this transporter.