Role of CCK-A receptor for pancreatic function in mice: a study in CCK-A receptor knockout mice.
BACKGROUND
The cholecystokinin (CCK) family of peptides and receptors is present throughout the brain and gastrointestinal tract. The CCK receptors can be pharmacologically subdivided into two subtypes: CCK-A and CCK-B. CCK-A receptor is enriched in the pancreas of mice.


OBJECTIVE
To determine pancreatic functions 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.


METHODS
To examine exocrine functions, amylase release from the dispersed acini in vitro was examined. In the in vivo study, the mixture of bile-pancreatic juice was collected, and amylase, bicarbonate, and bile acid outputs were determined after the administration of various stimulants. The cystic duct of the gallbladder and the pylorus were ligated to exclude the involvement of gallbladder contraction and gastric acid. Pancreatic enzyme content was measured, and histologic examinations by HE and lacZ staining were conducted. To examine endocrine functions, oral glucose tolerance test (2 g/kg) was determined.


RESULTS
The body weight, pancreatic wet weight, and enzyme content in the pancreas were similar among the three genotypes. Amylase release in vivo and in vitro and bicarbonate secretion in vivo were not stimulated by CCK-8 in CCK-AR (-/-) mice, whereas the responses to other stimulants were substantial in (-/-) mice. Administration of secretin did not increase bicarbonate secretion regardless of genotype. A normal glucose tolerance was observed in (-/-) mice. Acinar cells, islets, and duct cells were stained by lacZ, and HE staining revealed no pathologic findings.


CONCLUSIONS
The CCK-A receptor is important for pancreatic exocrine secretion, but not essential for maintaining glucose concentration and pancreatic growth in mice.
Takiguchi
Soichi
S
Division of Chemotherapy, National Kyushu Cancer Center, Minamiku Fukuoka, Japan.
Suzuki
Shinji
S
Sato
Yuko
Y
Kanai
Setsuko
S
Miyasaka
Kyoko
K
Jimi
Atsuo
A
Shinozaki
Hirotsugu
H
Takata
Yutaka
Y
Funakoshi
Akihiro
A
Kono
Akira
A
Minowa
Osamu
O
Kobayashi
Tomoko
T
Noda
Tetsuo
T
D000681:Amylases / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000032:analysis / Q000378:metabolism; D001646:Bile / Q000737:chemistry; D001647:Bile Acids and Salts / Q000032:analysis / Q000378:metabolism; D001839:Bombesin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005838:Genotype; D005951:Glucose Tolerance Test; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010189:Pancreatic Juice / Q000737:chemistry; D010446:Peptide Fragments / Q000494:pharmacology; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000172:deficiency* / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology
D001639:Bicarbonates; D001647:Bile Acids and Salts; D010446:Peptide Fragments; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; C040794:neuromedin C; D002217:Carbachol; D000681:Amylases; D012844:Sincalide; D001839:Bombesin