Common mechanisms of inhibition for the Na~2+/glucose(hSGLT1) and Na~+/Cl~-/GABA(hGAT1)cotransporters

摘要

Electrophysiological methods were used to investigate the interaction of inhibitors with the human Na~+/glucose(hSGLT1)and Na~+/Cl~-/GABA(hGAT1)cotransporters. Inhbitor constants were estimated from both inhibition of substrate-dependent current and inhibitor-induced changes in cotransporter conformation. The competitive, non-transported inhibitors are substrate derivatives with inhibition constants From 200 nM(phlorizin)to 17 mM(esculin)for hSGLT1, and 300 nM(SKF89976A)to 10 mM (baclofen)for hGAT1.