Specificity of classical and putative Cl(-) transport inhibitors on membrane transport pathways in human erythrocytes.
Culliford S., Ellory C., Lang HJ., Englert H., Staines H., Wilkins R.
The majority of anion transport inhibitors tend to be non-specific. This is problematic from a research point of view as caution is required when defining pathways purely based on pharmacology. Here we have tested a range of classical and putative Cl(-) transport inhibitors on three Cl(-) carrier systems (the KCl cotransporter (KCC), the NaK2Cl cotransporter (NKCC), and the Band 3 anion exchanger (AE)) found in human erythrocytes, using radiolabel tracer experiments. The study confirms the cross-reactivity of many anion transport inhibitors. However, two compounds, H25 and H156, were found to be both potent (IC(50) values < 0.1 mM) and specific (at least 1000-fold more effective against one carrier compared to the other two) inhibitors of NKCC and AE, respectively.