Colchicine inhibits the effects of secretin on pancreatic duct cell tubulovesicles and HC03 secretion in the pig

Secretin stimulation clears the cytoplasm of intralobular pancreatic duct cells in pigs of tubulovesicles and causes these cells to secrete HCO₃^- into the pancreatic juice. To determine whether the clearance of cytoplasmic tubulovesicles involves the microtubule system and is important for initiation of HCO₃^- secretion, the effect of the microtubule poison colchicine on duct cell morphology and pancreatic HCO₃^- secretion was measured in anaesthetized pigs. Before colchicine, secretin reduced the density of tubulovesicles in the cytoplasm of pancreatic duct cells from 92 ± 8 U to 8 ± 2 U and initiated pancreatic secretion of 176 ± 21 μmol min^-1 HCO₃^-. After colchicine, secretin failed to lower duct cell tubulovesicle density and caused the secretion of only 77 ± 14μmol min^-1 HCO₃^-. By contrast, lumicolchicine, an isomer of colchicine that does not affect microtubules, did not inhibit pancreatic HCO3 secretion. Colchicine did not reduce carbonic anhydrase or Na,K-ATPase activities in in-vitro assays. The clearance of tubulovesicles from the cytoplasm of pancreatic duct cells therefore seems to be microtubule-dependent and important for the pancreatic HCO₃^- secretion.