Functional characteristics and lysosomal integrity of the isolated perfused cat pancreas

Abstract

The isolated cat pancreas perfused with a physiological salt solution plus low molecular-weight dextran functions satisfactorally for at least 2 1 2 hours. Evidence for stability and functional integrity of the preparation included measurements of vascular resistance, arterial and venous pH, PO 2, and PCO 2, pancreatic juice volumes and trypsin concentrations, and studies of acinar cell ultrastructure. Total specific β-glucuronidase activity of the unstimulated perfused pancreas was comparable to that seen in the intact cat pancreas. However, pancreozymin and secretin decreased the total β-glucuronidase activity of the perfused pancreas. Pancreozymin also increased the release of β-glucuronidase from lysosomal suspensions of liver and pancreas. β-Glucuronidase activity rose in the pancreatic juice, duodenal secretion, perfusate, and the bathing medium of the hormonally stimulated perfused pancreas concomitant with a decreased number of zymogen granules and lysosomes in the acinar cells. The data are consistent with the hypothesis that pancreozymin increases the fragility of pancreatic lysosomes liberating β-glucuronidase into the pancreatic duct, extracellular space, and intravascular compartment. Lysosomal enzymes released into the duct may have an auxiliary digestive function in the duodenum, and the increased extracellular lysosomal enzyme activity may play a role in the pathophysiology of pancreatitis or other pancreatic disease states in which the pancreatic lysosomes become compromised.