Effects of Selected Drugs on Pancreatic Macromolecular Transport

Abstract

Abstract It is well known that pancreatic digestive proteins are synthesized on ribosomes attached to endoplasmic reticulum and that nascent proteins are transported through membranes of the endoplasmic reticulum into intracisternal spaces and thence into Golgi apparatus where condensation and encapsulation occur. Digestive proteins are stored in zymogen granules and secreted into pancreatic ductules after a secretory stimulus. This study was designed to examine effects of certain drugs on pancreatic protein synthesis, intracellular transport, and secretion. For these studies, pooled rat pancreatic slices were pulse-labeled with L-phenylalanine- 14 C and migration of the 14 C-labeled proteins studied by chase incubation for 15, 30, 60, and 120 min. After in vitro incubation, subcellular particles were isolated by density gradient centrifugation and specific activity of radioactive-labeled proteins determined in subcellular fractions. These studies indicate that bethanechol chloride did not alter the rate of transport of synthesized proteins from ribosomes into zymogen granules but increased the rate of secretion of proteins from zymogen granules into medium. Tetracycline and amphotericin B impaired transport of labeled proteins from microsomes to zymogen granules as well as secretion of labeled proteins from zymogen granules into medium. Puromycin did not alter either rate of transport of labeled proteins or secretion of labeled proteins into medium. Lidocaine increased appearance of unlabeled proteins into medium but significantly impaired secretion of labeled proteins. These studies provide information concerning fundamental mechanisms involved with transport, synthesis, and secretion of pancreatic digestive proteins.