Importance of CCK-A receptor for gallbladder contraction and pancreatic secretion: A study in CCK-A receptor knockout mice

Bile and pancreatic secretions were determined in a CCK-A receptor deficien t mouse mutant generated by gene targeting in embryonic stem cells. The tar geting vector contained lacZ and neo insertions in exon 2. Under the uretha ne anesthesia, the common bile duct was cannulated, and the mixture of bile -pancreatic juice was collected every 30 min. After the 1 h basal secretion , CCK-8 (0.5 and 1.0 nmol/kg), acetylcholine (500 nmol/kg), and neuromedin C (1.0 mu mol/kg) were injected subcutaneously, and the secretions were col lected following 1 h. Amylase and bile acid outputs were determined as para meters of pancreatic secretion and gallbladder contraction, respectively. I n some CCK-A receptor (+/-) animals, LacZ staining was performed. CCK-8 sig nificantly increased amylase and bile acid outputs in CCK-A receptor (+/+) and (+/-) mice, whereas no response was observed in (-/-) mice. Neuromedin C and acetylcholine increased amylase secretion in CCK-A receptor (-/-) mic e similar to (+/-) and (+/+) mice. The same doses of neuromedin C and acety lcholine could not increase bile acid secretion. The gallbladder smooth mus cles, pancreatic acinar cells, duct cells, and islets were stained by LacZ. CCK and CCK-A receptor are important for pancreatic secretion and gallblad der contraction. Neuromedin C and acetylcholine may compensate pancreatic f unction, but not gallbladder contraction.