Interference of tris(hydroxymethyl)aminomethane with structure and function of Golgi membranes.

Short term perfusion of isolated rat liver with tris(hydroxymethyl)aminomethane or other nonamphoteric amines (glycine amide, diethylamine) in moderate concentrations (10 to 20 micron) causes blistering of Golgi stacks on the concave side as well as swelling of lysosomes and of secretory vesicles in otherwise unaltered hepatocytes. Similar vacuolization is observed in Kupffer cells, pancreatic beta-cells, intestinal epithelial cells, and renal proximal tubule cells, but not in alpha-cells of the pancreas or in kidney glomerular podocytes. Fusion of the vesicles occurs frequently and involves denudation of intramembranous particles from contact areas. Since protein synthesis is not affected, inhibition by tris(hydroxymethyl)aminomethane of protein secretion into the perfusate indicates a block in protein processing at a postribosomal level. This finding together with morphologic evidence unravels the Golgi and post-Golgi membranes as specific site of tris(hydroxymethyl)aminomethane interaction with intracellular structures.