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 deficient mouse mutant generated by gene targeting in embryonic stem cells. The targeting vector contained lacZ and neo insertions in exon 2. Under the urethane 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 micromol/kg) were injected subcutaneously, and the secretions were collected following 1 h. Amylase and bile acid outputs were determined as parameters of pancreatic secretion and gallbladder contraction, respectively. In some CCK-A receptor (+/-) animals, LacZ staining was performed. CCK-8 significantly 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 (-/-) mice similar to (+/-) and (+/+) mice. The same doses of neuromedin C and acetylcholine could not increase bile acid secretion. The gallbladder smooth muscles, pancreatic acinar cells, duct cells, and islets were stained by LacZ. CCK and CCK-A receptor are important for pancreatic secretion and gallbladder contraction. Neuromedin C and acetylcholine may compensate pancreatic function, but not gallbladder contraction.