Effects of 5-fluorouracil on protein synthesis and secretion of the rat parotid gland.

100 mg/kg of FU were injected intraperitoneally once daily for three days. Animals were anaesthetized with 50 mg/kg of sodium pentobarbital before cannulation of the parotid duct. The total volume, amylase and protein content of the saliva were determined after stimulation with either 5 mg/kg pilocarpine or 5 mg/kg isoproterenol in FU-treated, pair-fed, and control animals. Saliva from FU-treated animals was significantly lower (p less than 0.05) in volume, amylase and protein content than that of both control groups. SDS, anionic and cationic gel electrophoresis of parotid saliva revealed no qualitative changes in the types of proteins secreted. FU reduced the total glandular amylase per unit DNA in both unstimulated and isoproterenol-stimulated parotids (p less than 0.05). Decreased protein synthesis may be the mechanism underlying the depleted secretory protein stores because the contents of isolated secretory granules from experimental glands contained less radiolabelled protein than those of either control group, and whole-gland homogenates had marked reductions in the activities of three lysosomal enzymes and in total RNA content. The secretory granules of experimental animals contained less labelled protein than those of controls, but experimental animals secreted a greater proportion of their total glandular radiolabelled secretory protein into saliva relative to amylase, suggesting that newly synthesized secretory proteins were preferentially secreted.