Effect of the microtubule-disrupting drug colchicine on rat cerulein-induced pancreatitis in comparison with the microtubule stabilizer taxol.
Effects of colchicine, a microtubule-disrupting agent, on rate exocrine pancreas were examined in comparison with the microtubule stabilizer Taxol for the purpose of analyzing the pathogenesis of cerulein-induced acute pancreatitis. Taxol ameliorated the inhibition of pancreatic secretion, elevation of serum amylase level, pancreatic edema, and histological alterations induced by supramaximal cerulein stimulation. In contrast, colchicine by itself and colchicine followed by cerulein stimulation (maximal and supramaximal) inhibited pancreatic secretion but did not induce the hyperamylasemia, pancreatic edema, or formation of large vacuoles, which characterized cerulein-induced pancreatitis. Electron microscopic studies in the colchicine-treated rats revealed that transport vesicles were accumulated in the supranuclear region and that no large vacuoles were observed in the apical lesion. Immunofluorescence studies confirmed that colchicine inhibited pancreatic secretion and disrupted the arrangement of microtubules. Posttreatment of colchicine did not prevent the development of cerulein-induced pancreatitis. Vinblastine, another microtubule-disrupting drug, as well as colchicine, inhibited pancreatic secretion but did not induce acute pancreatitis. The results obtained in this study suggest that microtubule disorganization at a specific step in the process of intracellular vesicular transport causes cerulein-induced pancreatitis and that this step is more apical than that at which colchicine inhibits secretion in the pancreatic acinar cell.
Ueda
T
T
First Department of Surgery, Kobe University School of Medicine, Japan.
Takeyama
Y
Y
Adachi
M
M
Toyokawa
A
A
Kishida
S
S
Yamamoto
M
M
Saitoh
Y
Y
D000208:Acute Disease; D000681:Amylases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002108:Ceruletide / Q000633:toxicity; D003078:Colchicine / Q000494:pharmacology*; D004195:Disease Models, Animal; D005765:Gastrointestinal Agents / Q000633:toxicity; D008297:Male; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology; D010189:Pancreatic Juice / Q000187:drug effects / Q000378:metabolism*; D010195:Pancreatitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014357:Trypsin / Q000187:drug effects / Q000378:metabolism; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism
D005765:Gastrointestinal Agents; D014404:Tubulin; D002108:Ceruletide; D000681:Amylases; D014357:Trypsin; D017239:Paclitaxel; D003078:Colchicine