Effects of intrapancreatic neuronal activation on cholecystokinin-induced exocrine secretion of isolated perfused rat pancreas

The role of intrapancreatic neurons in the action of cholecystokinin (CCK) on pancreatic exocrine secretion of the totally isolated, perfused rat panc reas was investigated. Intrapancreatic neurons were activated by applying e lectrical field stimulation (EFS) to the isolated pancreas for 45 min. When applying EFS, spontaneous pancreatic secretions of fluid and amylase incre ased until the second 15-min period of EFS and then decreased during the th ird 15-min period. Atropine (2 mu M) notably reduced the EFS-evoked pancrea tic secretions of fluid and amylase. The CCK-induced (10 pM) pancreatic sec retions of fluid and amylase elevated further in the first 15-min period of EFS and then gradually resumed to the levels observed during application o f CCK alone in the third 15-min period of EFS. However, the CCK-induced pan creatic secretions remained elevated even in the third 15-min period of EFS when an action of endogenous somate statin was inhibited by cycle-(7-amino heptanonyl-Phe-D-Trp-Lys-Thr[BZL]) (10 nM) or pertussis toxin (200 ng/ml). EFS further elevated spontaneous exocrine secretion by the cysteamine-treat ed (300 mg/kg) pancreas, but this was markedly reduced, to normal levels, b y infusing somatostatin (100 pM). EFS increased the numbers of immunoreacti ve somatostatin cells in the Langerhans' islets. The results indicate that intrapancreatic neuronal activation influences CCK-induced pancreatic secre tions in a dual-phase pattern in the rat: an increase during the early phas e and a decrease during the late phase. Endogenous somatostatin released fr om the islets appears to inhibit the enhancing effect of neuronal activatio n on CCK-induced pancreatic secretion. Of the intrapancreatic neurons, the cholinergic ones appear to predominate in EFS's effects on CCK-induced panc reatic secretion.