Characteristics of fluid secretion from isolated rat pancreatic ducts stimulated with secretin and bombesin.

1. Micropuncture techniques were used to study the cellular mechanisms of fluid secretion by interlobular ducts isolated from the pancreas of copper-deficient rats. 2. Perifusing ducts with a calcium-free buffer containing 5 mM-EGTA reduced the volume of fluid secreted in the presence of 10 nM-bombesin by 62%, whereas fluid secretion measured in the presence of 10 nM-secretin was reduced by only 26%. 3. The anion selectivities of the fluid secretions evoked by secretin and bombesin were different. The anion sequence for secretin was: Br- = I- = NO3- = Cl- (1.0) much greater than thiocyanate = gluconate (0.3); whereas the sequence for bombesin was: Br- = Cl- (1.0) greater than I- = NO3- (0.6) greater than thiocyanate = gluconate (approximately 0.3). 4. SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid; mM), reduced fluid secretion measured in the presence of bombesin by 61%, but had no effect on the response to secretin. 5. The K+ channel blockers, barium (3 mM) and tetraethylammonium (TEA; 10 mM), inhibited fluid secretion measured in the presence of both secretin and bombesin by between 52 and 66%. 6. From these results, we conclude that secretin and bombesin may utilize different intracellular signalling pathways and, furthermore, may activate different anion secretory mechanisms within the pancreatic ductal epithelium. However, the effect of the potassium channel blockers is consistent with both peptides activating secretory mechanisms which are electrogenic, and which depend for their operation on potassium efflux across the basolateral membrane of the duct cell.