Relative importance of cholecystokinin and cholinergic nerve mechanisms in the regulation of pancreatic secretion in rats

Several substances modulate the function of pancreatic acinar cells in vitro through specific receptors. All of them may also act in vivo, but the relative importance of their effect under physiological conditions is highly variable. The aim of this study was to assess the respective participation of cholinergic nerves and cholecystokinin (CCK) in the interdigestive pancreatic exocrine secretion and in the pancreatic response to intragastric or intraduodenal nutrients. Unanesthetized rats, equipped with a semichronic (5 days) pancreatic fistula, were used. They received a test-meal in the stomach (42 kJ) or the duodenum (21 kJ), and were infused intravenously with an antagonist of muscarinic (atropine, pirenzepin), nicotinic (hexamethonium), or CCK (L364718, lorglumide, Boc-Tyr(SO3)-Nle-Gly-D-Trp-Nle-Asp-NH-CH2-CH2-C6H5) receptors. Basal interdigestive pancreatic exocrine secretion decreased significantly after atropine, pirenzepine or hexamethonium. Protein output decreased more (peak inhibition 60 to 80 percent according to the drugs, p less than 0.01 to p less than 0.001) than volume or bicarbonate output (peak inhibition 25 to 65 percent according to the drugs, p less than 0.05 to p less than 0.01). CCK antagonists did not change the interdigestive pancreatic secretion. The cumulated response to the intraduodenal meal did not change after hexamethonium or pirenzepin, but increased after atropine (by approximately 50 percent, p less than 0.001 for volume and bicarbonate output, and nearly 100 percent, p less than 0.05 for protein output). The CCK antagonists entirely suppressed the protein response to the intraduodenal meal, decreased the volume response by 70 percent (p less than 0.01), and the bicarbonate response by 50 percent (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)