MALEATE MODIFIES APICAL ENDOCYTOSIS AND PERMEABILITY OF ENDOPLASMIC-RETICULUM MEMBRANES IN KIDNEY TUBULAR CELLS

Previous studies have shown that histochemical modifications of the en doplasmic reticulum in epithelial cells might be related to their tran sport function. We have examined the effect of sodium maleate, which p roduces generalized transport derangement reminiscent of Fanconi syndr ome, on the organization, morphology and enzyme activities of endoplas mic reticulum in rat kidney cells. The osmium impregnation technique h as revealed that apical vacuoles increase in volume and in number in m ost proximal tubule cells, and contain osmium deposits. Osmium impregn ation of the endoplasmic reticulum is much reduced. In vitro studies, performed with isolated microsomes, show NADPH cytochrome c reductase activity in both normal and maleate-treated rats. As revealed by vanad ate, Ca+-ATPase activity in isolated microsomes is unnaffected by male ate but the vanadate-insensitive or passive component of calcium uptak e increases particularly later in the response. Therefore, the remaini ng calcium uptake in the presence of vanadate is indeed passive; in vi vo maleate administration also appears to increase the passive entry o f calcium into the microsomal compartment. The morphological and histo chemical alterations of the endoplasmic reticulum cisternae occur rapi dly and with a similar time course to the transport defects, suggestin g that this organelle plays a role in transcellular transport. Maleate may directly affect the endoplasmic reticulum membranes whereby passi ve permeability to calcium is increased. The endocytotic apparatus and possibly exocytosis phenomena are modified by maleate as shown by the increased vacuolization and the presence of black osmium deposits in vacuoles.