<Original Articles>Lysosomal Enzyme Secretion into Pancreatic Juice in Rats Injected with Pancreatic Secretagogues and Augmentd Secretion after Short Term Pancreatic Duct Obstruction

Abstract

To examine the possible secretion of lysosomal enzymes into the pancreatic juice in rats stimulated with pancreatic secretagogues under both physiological and pathological conditions, we investigated the changes in the secretion of cathepsin B, as a lysosomal enzyme, into pancreatic juice with stimulation of 5 different doses (0. 1, 0. 2, 0. 5, 1. 0 , and 1. 5 μg/kg ・ hr) of caerulein . Control rats had only pancreatic duct cannulation . In other rats, the pancreatic duct was obstructed for 3 hours and secretin was infused (0. 2 CU/kg ・ hr). Caerulein stimulated the secretion of cathepsin B into the pacreatic juice in a dose-dependent manner, as in amylase secretion, and caerulein in higher doses (1. O and 1. 5 μg/kg ・ hr) inhibited cathepsin B output as it did amylase output. There was a significantly high positive correlation between cathepsin B output and amylase output after stimulation with caerulein. The secretion of several other lysosomal enzymes was also stimulated by caerul ein . Blockage of the pancreatic duct for 3 hours caused a significant but moderate rise in serum amylase levels. Redistribution of cathepsin B activity in the pancreatic subcellular fractions was noted with an increase in the amount of cathepsin B recovered from zymogen-rich pellets after 15 min of centrifugation at 1300 × g. These changes after temporary pancreatic duct obstruction are very similar to those previously noted during the early stage of diet-and caerulein-induced experimental pancreatitis and suggest colocalization oflysosomal enzymes and digestive enzymes. In addition, in ductobstructed rats, the secretion of cathepsin B and other lysosomal enzymes stimulated by caerulein was significantly greater than in animals with free-flowing pancreatic juice. These results indicate that lysosomal enzymes are secreted into pancreatic juice after stimulation by gut hormones in the same manner as classical pancreatic diges ti ve enzymes such as amylase. Moreover, lysosomal enzymes which colocalize with zymogen granul es in rats with short-term pancreatic duct obstruction are also secreted into pancreratic juice together with digestive enzymes after stimulation with gut hormones. These findings suggest that lysosomal enzymes are present in zymogen granules under normal conditions and that they may play pathophysiological roles in pancreatic juice. They also contribute to an understanding of thepathogenesis of pancreatitis, since cathepsin B can activate trypsinogen.

ラット膵液中へのライソゾーム酵素分泌動態を解明する目的にて、 caerulein (0. 1 - 1. 5 ug/Kg ・ hr)の刺激下および3時間の膵管閉塞後の cathepsin B 分泌動態を検討した。caerulein 刺激下での cathepsin B 分泌動態は膵酵素である amylase とほぼ同様の分泌動態を示すとともに amylase 分泌量と高い正の相関関係を示した。3時間の膵管閉塞後にはコントロール群に比べ caerulein 刺激下、より大量の cathepsin B を含むライソゾーム酵素の存在を示すとともに、消化管ホルモンを介した膵液中へのライソゾーム酵素の分泌をも示すものであった。さらに短期間の膵管閉塞後には膵液中へのライソゾーム酵素の分泌が増加し、cathepsin B は trypsinogen を活性化し得ることより、胆石性膵炎等による膵管閉塞後には、膵管腟での膵消化酵素の活性化にも十分注意を払う必要があるものと考えられた。