Distribution of a Synthetic Protease Inhibitor in Rat Pancreatic Acini After Supramaximal Secretagogue Stimulation
作者:
Taiichi Otani,
Yutaka Atomi,
Akira Kuroda,
Tetsuichiro Muto,
Masaro Tamura,
Satoru Fukuda,
Shuichi Akao,
Fred Gorelick,
期刊:
Pancreas
(OVID Available online 1997)
卷期:
Volume 14,
issue 2
页码: 142-149
ISSN:0885-3177
年代: 1997
出版商: OVID
关键词: Synthetic protease inhibitor;Electron microscopic autoradiography;Isolated pancreatic acini;Cerulein stimulation;Rat
数据来源: OVID
摘要:
Protease inhibitors may have a beneficial effect in acute pancreatitis. The effects of E3123, a new low molecular weight protease inhibitor, on the ultrastructure of isolated pancreatic acini were examined using transmission electron microscopy. Acini supramaximally stimulated with cerulein (10−8M) formed large cytoplasmic vacuoles similar to those generated in the cerulein-induced in vivo model of pancreatitis. Pretreatment of isolated acini with E3123 significantly reduced the size and number of vacuoles associated with cerulein treatment. The distribution of3H-E3123 in acinar cells was examined using a pulse-chase protocol and electron microscopic autoradiography. Cellular levels of3H-E3123 increased about 30-fold in acinar cells treated with cerulein (10−8M) compared to unstimulated controls. In cerulein-treated acini examined after a 5-min chase, 47.4% of the autoradiographic grains were associated with the rough endoplasmic reticulum and 13.2% were associated with zymogen granules. After 30 min of incubation, the grains associated with the endoplasmic reticulum decreased to 18.5% but increased to 26.3% over zymogen granules. Thus, E3123 is taken up by the acinar cell and follows a cellular itinerary similar to that of newly synthesized secretory proteins. One potential conclusion from these studies is that the ability of E3123 to reduce the formation of vacuoles in supramaximally stimulated acini may be due to its inhibition of proteases within the secretory pathway.
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