Synthesis of intestinal clycoproteins inhibition of [1- 14C]glucosamine incorporation by sodium salicylate in vitro

Abstract

1. 1. Sodium salicylate at concentrations of 7.5 mM and 15.0 mM inhibited incorporation of [I- 14C]glucosamine into glycoprotein by slices of rat small intestine. This inhibition was dose dependant and not due to an inhibition of glucosamine uptake by the intestinal mucosa. It was also unaffected by the concentration of glucosamine in the incubation medium. 2. 2. A comparison of the effect of sodium salicylate on both [1- 14C]glucosamine and L-[U- 14C]leucine incorporation revealed that leucine incorporation was more markedly inhibited at early time periods. These results indicate that the inhibition of glucosamine incorporation may in part result from a reduced synthesis of peptide acceptor. 3. 3. The addition of salicylate to slices in which protein synthesis had been reduced to 2.0% by cycloheximide resulted in an additional 38% inhibition of glucosamine incorporation. 4. 4. Radioactive free glucosamine was increased in acid-soluble intermediates of slices exposed to salicylate and cycloheximide as compared to those exposed to cycloheximide alone, while radioactivity in acetylated acid soluble intermediates was decreased. 5. 5. Salicylate therefore inhibits the incorporation of glucosamine which occurs independently of protein synthesis, and thus appears to have a specific inhibitory effect on oligosaccharide assembly. Inhibition primarily effects acetylation of glucosamine.