Inhibitory effect of bile salts on gallbladder smooth muscle contractility in the guinea pig in vitro

Chen, Nansheng; Freedman, SM; Shaffer, E.A.

doi:10.1016/s0016-5085(97)70053-2

Cited by 38 publications

(33 citation statements)

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“…Indeed, candidate transport proteins for cholesterol, such as ABCG5/G8 (35), scavenger receptor class B type I (36), and megalin (37), have been detected in the human gallbladder wall. Alternatively, hydrophobic bile salts such as deoxycholate may impair gallbladder motility (38). Indeed, in the current study, hydrophobic bile salts (taurodeoxycholate and taurochenodeoxycholate) were found in appreciable amounts exclusively in C57L mice.…”

Section: Discussionmentioning

confidence: 44%

Gallbladder histopathology during murine gallstone formation: relation to motility and concentrating function

Erpecum

Wang

Moschetta

et al. 2006

Journal of Lipid Research

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C57L mice are susceptible and AKR mice are resistant to gallstone formation. We studied in male mice of both strains gallbladder histopathology, cholecystokinininduced emptying, and concentrating function at 0, 14, 28, and 56 days on a lithogenic diet. Gallbladder wall thickness increased on the diet, with stromal granulocyte infiltration, progressive fibrosis, edema, and epithelial cell indentation, particularly in C57L. Strong basal cholecystokinin octapeptide-induced gallbladder emptying (70% of fasting volumes) occurred in both strains, but fasting gallbladder volumes were significantly larger in C57L (14.8 6 2.2 ml vs. 8.8 6 1.0 ml). On the diet, fasting volumes increased exclusively in C57L (28.6 6 2.9 ml on day 56), with progressively decreased emptying (27% of fasting volumes on day 56). Gallbladder emptying remained normal in AKR. Gallbladder concentrating function decreased on the lithogenic diet (especially in C57L), coinciding with decreased aquaporin-1 (AQP1) and AQP8 expression at the mRNA and protein levels. In additional experiments, similar downregulation of AQP1 and AQP8 mRNA expression occurred in farnesoid X receptor (FXR)-deficient mice after 1 week on the lithogenic diet, without any difference from corresponding wild-type mice. In conclusion, during murine lithogenesis, altered gallbladder histology is associated with impaired motility, reduced concentrating function, and decreased AQP1 and AQP8 expression, the latter without the involvement of the FXR. Supplementary key words aquaporin . cholesterol . farnesoid X receptor . gallbladder emptying . water channel C57L and AKR inbred mice exhibit different susceptibilities to cholesterol gallstone formation, depending on Lith genes. Susceptibility is high in C57L males (gallstones in 80% of mice after 56 days on a lithogenic diet) and low in AKR males (gallstones in 15% after 56 days on a lithogenic diet) (1). Based on their time course during the earliest stages of lithogenesis, biliary cholesterol supersaturation, the hydrophobic bile salt deoxycholate, and high concentrations of crystallization-promoting mucin are thought to play crucial roles in murine gallstone formation (1, 2). In humans, the gallbladder is thought to be another key player in gallstone pathogenesis. Impaired postprandial and interdigestive gallbladder emptying are often found in gallstone patients, providing time for nucleation of cholesterol crystals and their aggregation into macroscopic stones (3). Also in animal models, gallbladder contractility is decreased in the earliest stages of gallstone formation, even before gallstones have formed (4). Furthermore, in the fasting gallbladder, hepatic bile is concentrated 4-to 5-fold by absorption of water, thereby enhancing cholesterol crystallization (5, 6). Aquaporins (AQP0 to AQP10) are a family of transmembrane channels mediating the movement of water through the lipid bilayer. AQP1 (7-12) and AQP8 (12) have recently been detected in gallbladder epithelial cells. Virtually no information is available about the g...

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Section: Discussionmentioning

confidence: 44%

Gallbladder histopathology during murine gallstone formation: relation to motility and concentrating function

Erpecum

Wang

Moschetta

et al. 2006

Journal of Lipid Research

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“…Alternatively, CDCA enrichment may have altered gall bladder contractility in response to a meal stimulus because CDCA has been shown to inhibit gall bladder muscle cell contraction in vitro induced by agonists CCK-8, ACh, and KCl. 29,30 Future studies will address the impact of CDCA supplementation on cholecystokinin secretion and gall bladder contraction. 30,31 In agreement with previous studies, DCA supplementation resulted in a considerable increase in intralumenal DCA, whereas peak total bile acid concentrations were not significantly altered after a meal stimulus.…”

Section: Discussionmentioning

confidence: 99%

Hypoglycemic and insulin-sensitizing effects of berberine in high-fat diet- and streptozotocin-induced diabetic rats

et al. 2011

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“…In addition, bile acids (30-300 M) have been shown to relax gallbladder smooth muscle (Sunagane et al, 1990;Xu et al, 1997), intestine (Sunagane et al, 1986), and uterus (Uruno et al, 1975). However, the cellular and molecular mechanisms underlying this widespread, nonspecific relaxation of smooth muscle by bile acids are not well understood.…”

Section: Possible Role Of Bile Acid Activation Of Bk Ca Channels In Bmentioning

confidence: 99%

Natural Bile Acids and Synthetic Analogues Modulate Large Conductance Ca2+-activated K+ (BKCa) Channel Activity in Smooth Muscle Cells

Dopico

2002

The Journal of General Physiology

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Bile acids have been reported to produce relaxation of smooth muscle both in vitro and in vivo . The cellular mechanisms underlying bile acid-induced relaxation are largely unknown. Here we demonstrate, using patch-clamp techniques, that natural bile acids and synthetic analogues reversibly increase BK Ca channel activity in rabbit mesenteric artery smooth muscle cells. In excised inside-out patches bile acid-induced increases in channel activity are characterized by a parallel leftward shift in the activity-voltage relationship. This increase in BK Ca channel activity is not due to Ca 2 ϩ -dependent mechanism(s) or changes in freely diffusible messengers, but to a direct action of the bile acid on the channel protein itself or some closely associated component in the cell membrane. For naturally occurring bile acids, the magnitude of bile acid-induced increase in BK Ca channel activity is inversely related to the number of hydroxyl groups in the bile acid molecule. By using synthetic analogues, we demonstrate that such increase in activity is not affected by several chemical modifications in the lateral chain of the molecule, but is markedly favored by polar groups in the side of the steroid rings opposite to the side where the methyl groups are located, which stresses the importance of the planar polarity of the molecule. Bile acidinduced increases in BK Ca channel activity are also observed in smooth muscle cells freshly dissociated from rabbit main pulmonary artery and gallbladder, raising the possibility that a direct activation of BK Ca channels by these planar steroids is a widespread phenomenon in many smooth muscle cell types. Bile acid concentrations that increase BK Ca channel activity in mesenteric artery smooth muscle cells are found in the systemic circulation under a variety of human pathophysiological conditions, and their ability to enhance BK Ca channel activity may explain their relaxing effect on smooth muscle.

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Inhibitory effect of bile salts on gallbladder smooth muscle contractility in the guinea pig in vitro

Cited by 38 publications

References 1 publication

Gallbladder histopathology during murine gallstone formation: relation to motility and concentrating function

Gallbladder histopathology during murine gallstone formation: relation to motility and concentrating function

Hypoglycemic and insulin-sensitizing effects of berberine in high-fat diet- and streptozotocin-induced diabetic rats

Natural Bile Acids and Synthetic Analogues Modulate Large Conductance Ca2+-activated K+ (BKCa) Channel Activity in Smooth Muscle Cells

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