SIDE-SPECIFIC TOXIC EFFECTS ON THE MEMBRANES OF CULTURED RENAL EPITHELIAL-CELLS (A6)

A cultured epithelial cell line from toad kidney (A6) was used to inve stigate side-specific toxicity related to the apical (outer) and basol ateral (inner) membranes of epithelia. Well-known inhibitors and stimu lators of ion transport were used to show that the ion transport prote ins are asymmetrically distributed: the apical membrane contains sodiu m and chloride channels and the basolateral membrane contains Na+/K+ p umps, Na+/Cl- co-transporters, potassium channels and receptors for an tidiuretic hormone. The data demonstrate that the cellular toxicity of chemicals decreases when they are added to the apical side, illustrat ing that the epithelium acts as a functional barrier. However, the sid e-specific toxicity was more pronounced for ions and water-soluble mol ecules than for organic solvents, indicating that A6 epithelia can be used to distinguish between drugs that target specific membrane protei ns and those that target membrane lipids. Furthermore, the cell line c ould be used to pick up chemicals that, at low concentrations, inhibit sodium absorption and chloride secretion, without having any effect o n cellular toxicity.