Colchicine Inhibits the Effects of Secretin on Pancreatic Duct Cell Tubulovesicles and HCO3- 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 mumols min-1 HCO3-. After colchicine, secretin failed to lower duct cell tubulovesicle density and caused the secretion of only 77 +/- 14 mumols 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.