Age-associated Gallstone Formation in Male and Female CCK-1(A) Receptor-deficient Mice

Overview

Journal J Gastroenterol

Specialty Gastroenterology

Date 2007 Aug 3

PMID 17671765

Citations 1

Authors

Kyoko Miyasaka

Setsuko Kanai

Minoru Ohta

Hiroko Hosoya

Ayako Sekime

Saeko Akimoto

Soichi Takiguchi

Akihiro Funakoshi

Affiliations

Soon will be listed here.

Abstract

Background: Gallbladder dysmotility accelerates cholelithiasis. In turn, gallbladder dysmotility can occur secondary to inflammation and excess cholesterol accumulation in gallbladder smooth muscle.

Methods: The present study was designed to determine how much gallbladder dysmotility contributes to gallstone formation as a primary cause and whether a sex difference exists in gallstone formation by comparing cholecystokinin-1 receptor gene-deficient [CCK-1R(-/-)] male and female mice.

Results: No sludge or gallstone formation was observed in mice at 6 months of age. The frequency of sludge and gallstone formation in mice at 12 and 24 months of age was slightly higher in female CCK-1R(-/-) mice than in males, but the difference was not significant.

Conclusions: Gallbladder dysmotility may have accelerated sludge and gallstone formation, but its contribution was limited. A 12-month period was required to produce gallstones, and after the mice reached 12 months of age, further ageing did not increase the frequency of gallstones. The effect of sex did not reach a significant level.

Citing Articles

The Role of Cholecystokinin in Peripheral Taste Signaling in Mice.

Yoshida R, Shin M, Yasumatsu K, Takai S, Inoue M, Shigemura N Front Physiol. 2017; 8:866.

PMID: 29163209 PMC: 5671461. DOI: 10.3389/fphys.2017.00866.

References

Kopin A, Mathes W, McBride E, Nguyen M, Schmitz F, Bonner-Weir S . The cholecystokinin-A receptor mediates inhibition of food intake yet is not essential for the maintenance of body weight. J Clin Invest. 1999; 103(3):383-91. PMC: 407901. DOI: 10.1172/JCI4901. View

Cirillo D, Wallace R, Rodabough R, Greenland P, LaCroix A, Limacher M . Effect of estrogen therapy on gallbladder disease. JAMA. 2005; 293(3):330-9. DOI: 10.1001/jama.293.3.330. View

Xiao Z, Chen Q, Biancani P, Behar J . Mechanisms of gallbladder hypomotility in pregnant guinea pigs. Gastroenterology. 1999; 116(2):411-9. DOI: 10.1016/s0016-5085(99)70139-3. View

Miyasaka K, Takata Y, Funakoshi A . Association of cholecystokinin A receptor gene polymorphism with cholelithiasis and the molecular mechanisms of this polymorphism. J Gastroenterol. 2003; 37 Suppl 14:102-6. DOI: 10.1007/BF03326426. View

Takiguchi S, Suzuki S, Sato Y, Kanai S, Miyasaka K, Jimi A . Role of CCK-A receptor for pancreatic function in mice: a study in CCK-A receptor knockout mice. Pancreas. 2002; 24(3):276-83. DOI: 10.1097/00006676-200204000-00011. View

Sato N, Miyasaka K, Suzuki S, Kanai S, Ohta M, Kawanami T . Lack of cholecystokinin-A receptor enhanced gallstone formation: a study in CCK-A receptor gene knockout mice. Dig Dis Sci. 2003; 48(10):1944-7. DOI: 10.1023/a:1026110002713. View

Syngal S, Coakley E, Willett W, Byers T, Williamson D, Colditz G . Long-term weight patterns and risk for cholecystectomy in women. Ann Intern Med. 1999; 130(6):471-7. DOI: 10.7326/0003-4819-130-6-199903160-00003. View

Wang D, Paigen B, Carey M . Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: physical-chemistry of gallbladder bile. J Lipid Res. 1997; 38(7):1395-411. View

Wang D, Schmitz F, Kopin A, Carey M . Targeted disruption of the murine cholecystokinin-1 receptor promotes intestinal cholesterol absorption and susceptibility to cholesterol cholelithiasis. J Clin Invest. 2004; 114(4):521-8. PMC: 503765. DOI: 10.1172/JCI16801. View

10.

Chen Q, Amaral J, Oh S, Biancani P, Behar J . Gallbladder relaxation in patients with pigment and cholesterol stones. Gastroenterology. 1997; 113(3):930-7. DOI: 10.1016/s0016-5085(97)70189-6. View

11.

Fossati P, PRENCIPE L . Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem. 1982; 28(10):2077-80. View

12.

Noble F, Wank S, Crawley J, Bradwejn J, Seroogy K, Hamon M . International Union of Pharmacology. XXI. Structure, distribution, and functions of cholecystokinin receptors. Pharmacol Rev. 1999; 51(4):745-81. View

13.

Lee S . Gallstones: how do we translate an old story into future therapy?. Nat Clin Pract Gastroenterol Hepatol. 2005; 1(1):2-3. DOI: 10.1038/ncpgasthep0017. View

14.

Lammert F, Carey M, Paigen B . Chromosomal organization of candidate genes involved in cholesterol gallstone formation: a murine gallstone map. Gastroenterology. 2001; 120(1):221-38. DOI: 10.1053/gast.2001.20878. View

15.

Kajiyama G . [Etiology and clinical presentation of cholesterol cholelithiasis]. Nihon Naika Gakkai Zasshi. 2000; 89(9):1728-37. View

16.

Suzuki S, Takiguchi S, Sato N, Kanai S, Kawanami T, Yoshida Y . Importance of CCK-A receptor for gallbladder contraction and pancreatic secretion: a study in CCK-A receptor knockout mice. Jpn J Physiol. 2001; 51(5):585-90. DOI: 10.2170/jjphysiol.51.585. View

17.

Shoda J, He B, Tanaka N, Matsuzaki Y, Osuga T, Yamamori S . Increase of deoxycholate in supersaturated bile of patients with cholesterol gallstone disease and its correlation with de novo syntheses of cholesterol and bile acids in liver, gallbladder emptying, and small intestinal transit. Hepatology. 1995; 21(5):1291-302. View

18.

ALLAIN C, Poon L, Chan C, Richmond W, Fu P . Enzymatic determination of total serum cholesterol. Clin Chem. 1974; 20(4):470-5. View

19.

Xiao Z, Chen Q, Amaral J, Biancani P, Jensen R, Behar J . CCK receptor dysfunction in muscle membranes from human gallbladders with cholesterol stones. Am J Physiol. 1999; 276(6):G1401-7. DOI: 10.1152/ajpgi.1999.276.6.G1401. View

20.

Sharma B, Agarwal D, Dhiman R, Baijal S, Choudhuri G, Saraswat V . Bile lithogenicity and gallbladder emptying in patients with microlithiasis: effect of bile acid therapy. Gastroenterology. 1998; 115(1):124-8. DOI: 10.1016/s0016-5085(98)70373-7. View