Effect of the microtubule-disrupting drug colchicine on rat cerulein-induced pancreatitis in comparison with the microtubule stabilizer taxol. 1995

T Ueda, and Y Takeyama, and M Adachi, and A Toyokawa, and S Kishida, and M Yamamoto, and Y Saitoh
First Department of Surgery, Kobe University School of Medicine, Japan.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008854 Microscopy, Electron Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen. Electron Microscopy
D008856 Microscopy, Fluorescence Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye. Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D008870 Microtubules Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS. Microtubule
D010189 Pancreatic Juice The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. Juice, Pancreatic,Juices, Pancreatic,Pancreatic Juices
D010195 Pancreatitis INFLAMMATION of the PANCREAS. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of CHRONIC PANCREATITIS (International Symposium on Acute Pancreatitis, Atlanta, 1992). The two most common forms of acute pancreatitis are ALCOHOLIC PANCREATITIS and gallstone pancreatitis. Acute Edematous Pancreatitis,Acute Pancreatitis,Pancreatic Parenchyma with Edema,Pancreatic Parenchymal Edema,Pancreatitis, Acute,Pancreatitis, Acute Edematous,Peripancreatic Fat Necrosis,Acute Edematous Pancreatitides,Acute Pancreatitides,Edema, Pancreatic Parenchymal,Edematous Pancreatitides, Acute,Edematous Pancreatitis, Acute,Fat Necrosis, Peripancreatic,Necrosis, Peripancreatic Fat,Pancreatic Parenchymal Edemas,Pancreatitides, Acute,Pancreatitides, Acute Edematous,Parenchymal Edema, Pancreatic,Peripancreatic Fat Necroses
D002108 Ceruletide A specific decapeptide obtained from the skin of Hila caerulea, an Australian amphibian. Caerulein is similar in action and composition to CHOLECYSTOKININ. It stimulates gastric, biliary, and pancreatic secretion; and certain smooth muscle. It is used in paralytic ileus and as diagnostic aid in pancreatic malfunction. Caerulein,Cerulein,Ceruletid,FI-6934,Takus,FI 6934,FI6934
D003078 Colchicine A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (PERIODIC DISEASE). Colchicine, (+-)-Isomer,Colchicine, (R)-Isomer
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005765 Gastrointestinal Agents Drugs used for their effects on the gastrointestinal system, as to control gastric acidity, regulate gastrointestinal motility and water flow, and improve digestion. Digestants,Gastric Agents,Gastric Drugs,Gastrointestinal Drugs,Agents, Gastric,Agents, Gastrointestinal,Drugs, Gastric,Drugs, Gastrointestinal

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