Abstract
The synthetic compound N-cyanosulphonamide S0859 has been described as a selective inhibitor of sodium-bicarbonate cotransporters (NBC, SLC4) in mammalian heart (Ch'en et al., 2008). First, for comparison, the electrogenic human NBCe1 (SLC4A4) was heterologously expressed in Xenopus laevis oocytes, where its transport activity was inhibited by S0859 with an IC50 of 9µM. The activity of monocarboxylate transporter (MCT) isoforms 1, 2, and 4 (SLC16A1, SLC16A7, SLC16A3), which transport lactate, pyruvate and ketone bodies, were also heterologously expressed in Xenopus oocytes, and their transport activity was similarly and reversibly inhibited by S0859 with an IC50 of 4–10µM. Partial inhibition of lactate transport by S0859 (50µM) was also obtained in cultured astrocytes of mice. Thus, S0859 appears to be an inhibitor of anion transport with a broader spectrum than previously thought, and may also interfere with cellular metabolite uptake/release.
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