Lack of cholecystokinin-A receptor enhanced gallstone formation: a study in CCK-A receptor gene knockout mice.
The etiology of gallstones is multifactorial, with interactions between genes and the environment. We generated cholecystokinin (CCK) -A receptor (R)-deficient (-/-) mice and found that CCK did not produce gallbladder contraction in CCK-AR(-/-) mice. The purpose of this study was to identify the role of CCK-AR on gallstone formation. Age-matched CCK-AR gene (+/+) and (-/-) progenies were used. Sludge and gallstone formation, as well as plasma cholesterol levels, were measured at 12 and 24 months of age. Sludge and gallstone formation were significantly higher in CCK-AR(-/-) mice than in CCK-AR(+/+) mice at 12 and 24 months of age, although these were not different between 12 and 24 months of age. The plasma cholesterol levels, daily food intake, and body weight were not significantly different between CCK-AR(+/+) and (-/-) mice. Sludge and gallstone formation were not observed at 6 months of age. In conclusion, deteriorated gallbladder contraction due to a lack of CCK-AR favored gallstone formation after the middle age of life.
Sato
Norikazu
N
Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashiku, Tokyo-173-0015, Japan.
Miyasaka
Kyoko
K
Suzuki
Shinji
S
Kanai
Setsuko
S
Ohta
Minoru
M
Kawanami
Takako
T
Yoshida
Yuki
Y
Takiguchi
Soichi
S
Noda
Tetsuo
T
Takata
Yutaka
Y
Funakoshi
Akihiro
A
D000818:Animals; D005704:Gallbladder / Q000187:drug effects / Q000503:physiopathology; D042882:Gallstones / Q000209:etiology*; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D043886:Receptor, Cholecystokinin A / Q000172:deficiency*; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology*
C090019:8-sulfocholecystokinin octapeptide; D043886:Receptor, Cholecystokinin A; D012844:Sincalide