Side-specific toxic effects on the membranes of cultured renal epithelial cells (A6)

By Bjerregaard, H.F.

A cultured epithelial cell line from toad kidney (A6) was used to investigate side-specific toxicity related to the apical (outer) and basolateral (inner) membranes of epithelia. Well-known inhibitors and stimulators of ion transport were used to show that the ion transport proteins are asymmetrically distributed: the apical membrane contains sodium and chloride channels and the basolateral membrane contains Na+/K+ pumps, Na+/Cl- co-transporters, potassium channels and receptors for antidiuretic hormone. The data demonstrate that the cellular toxicity of chemicals decreases when they are added to the apical side, illustrating that the epithelium acts as a functional barrier. However, the side-specific toxicity was more pronounced for ions and water-soluble molecules than for organic solvents, indicating that A6 epithelia can be used to distinguish between drugs that target specific membrane proteins and those that target membrane lipids. Furthermore, the cell line could be used to pick up chemicals that, at low concentrations, inhibit sodium absorption and chloride secretion, without having any effect on cellular toxicity.