Gallbladder contraction in patients with pigment and cholesterol stones

Behar, José; Lee, Kwang Y.; Thompson, William R.; Biancani, Piero

doi:10.1016/0016-5085(89)90392-2

Cited by 150 publications

(106 citation statements)

References 30 publications

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“…14 A large body of evidence has shown reduced muscle contractility after stimulation by CCK in gallbladders with cholesterol gallstones. 5,13 These findings are in agreement with a study that showed that gallbladders with cholesterol stones had significantly lower levels of 125 I-labeled CCK-8 binding to receptors, suggesting that there may be fewer CCK-1 receptors (CCK-1 R) available for binding on the PM. 15 However, the defect in contraction can be corrected when PM receptors are bypassed by stimulation with G protein activator or secondary messengers such as diacylglycerol.…”

Section: Gallbladder Motilitysupporting

confidence: 87%

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Cholesterol gallstone disease: focusing on the role of gallbladder

Chen

Kong

2015

Laboratory Investigation

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Gallstone disease (GSD) is one of the most common biliary tract diseases worldwide in which both genetic and environmental factors have roles in its pathogenesis. Biliary cholesterol supersaturation from metabolic defects in the liver is traditionally seen as the main pathogenic factor. Recently, there have been renewed investigative interests in the downstream events that occur in gallbladder lithogenesis. This article focuses on the role of the gallbladder in the pathogenesis of cholesterol GSD (CGD). Various conditions affecting the crystallization process are discussed, such as gallbladder motility, concentrating function, lipid transport, and an imbalance between pro-nucleating and nucleation inhibiting proteins.

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Section: Gallbladder Motilitysupporting

confidence: 87%

“…12 However, gallbladders with pigment stones do not develop defects in contraction like those seen with cholesterol gallstones. 13 Taken together, these findings suggest that impaired gallbladder motility is an important contributing factor in CGD.…”

Section: Gallbladder Motilitymentioning

confidence: 83%

Cholesterol gallstone disease: focusing on the role of gallbladder

Chen

Kong

2015

Laboratory Investigation

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“…49 In contrast, gall bladders from patients having pigment gallstones had normal responses to this hormone. 49,50 A major difference between these two clinical settings is the presence of supersaturated cholesterol in lithogenic bile. 51 It was postulated that the cholesterol could get into the membrane and be responsible for the gall bladder muscle dysfunction.…”

Section: Lateral Allosterism Of Membrane Receptorsmentioning

confidence: 97%

“…48 Indeed, the first indication that this could be relevant to the CCK1R came from a set of observations in patients with cholesterol gallstones. 49 It was shown that gall bladders from such patients had abnormal contractile responses to CCK. 49 In contrast, gall bladders from patients having pigment gallstones had normal responses to this hormone.…”

Section: Lateral Allosterism Of Membrane Receptorsmentioning

confidence: 99%

“…49 It was shown that gall bladders from such patients had abnormal contractile responses to CCK. 49 In contrast, gall bladders from patients having pigment gallstones had normal responses to this hormone. 49,50 A major difference between these two clinical settings is the presence of supersaturated cholesterol in lithogenic bile.…”

Section: Lateral Allosterism Of Membrane Receptorsmentioning

confidence: 99%

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Cholecystokinin-induced satiety, a key gut servomechanism that is affected by the membrane microenvironment of this receptor

et al. 2016

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The gastrointestinal (GI) tract has a central role in nutritional homeostasis, as location for food ingestion, digestion and absorption, with the gut endocrine system responding to and regulating these events, as well as influencing appetite. One key GI hormone with the full spectrum of these activities is cholecystokinin (CCK), a peptide released from neuroendocrine I cells scattered through the proximal intestine in response to fat and protein, with effects to stimulate gall bladder contraction and pancreatic exocrine secretion, to regulate gastric emptying and intestinal transit, and to induce satiety. There has been interest in targeting the type 1 CCK receptor (CCK1R) for drug development to provide non-caloric satiation as an aid to dieting and weight loss; however, there have been concerns about CCK1R agonists related to side effects and potential trophic impact on the pancreas. A positive allosteric modulator (PAM) of CCK action at this receptor without intrinsic agonist activity could provide a safer and more effective approach to long-term administration. In addition, CCK1R stimulus-activity coupling has been shown to be negatively affected by excess membrane cholesterol, a condition described in the metabolic syndrome, thereby potentially interfering with an important servomechanism regulating appetite. A PAM targeting this receptor could also potentially correct the negative impact of cholesterol on CCK1R function. We will review the molecular basis for binding natural peptide agonist, binding and action of small molecules within the allosteric pocket, and the impact of cholesterol. Novel strategies for taking advantage of this receptor for the prevention and management of obesity will be reviewed.International Journal of Obesity Supplements (2016) 6, S22-S27; doi:10.1038/ijosup.2016.5 INTRODUCTIONThe prevalence of obesity has been progressively increasing throughout the United States and around the world, contributing to a parallel increase in the prevalence of type 2 diabetes mellitus and its associated comorbidities. 1 These problems have been responsible for extraordinary morbidity, suffering, loss in productivity and premature mortality. In spite of major efforts to develop effective weight reduction diets, diet aids, medications, medical devices and surgical procedures, the trajectory for this continues in the wrong direction. Bariatric surgery has proven to be quite effective in patients with morbid obesity; 2 however, this is quite expensive and not scalable, certainly not keeping up with the increasing prevalence of the most severe end of this clinical continuum. The activity of acute dieting and exercise has been similarly effective in inducing weight loss; however, it has not been durable, with an extremely high incidence of regaining weight to or even beyond the starting point. After a long hiatus in approved drugs, three new diet medications have recently been approved, 3-5 but all carry concerns about safety, and there are requirements for registration and careful clinical follow-up, re...

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Biochemical and morphological correlations in human gallbladder with reference to membrane permeability

Hopwood¹,

Ross²

1997

Microsc. Res. Tech.

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Gallbladder contraction in patients with pigment and cholesterol stones

Cited by 150 publications

References 30 publications

Cholesterol gallstone disease: focusing on the role of gallbladder

Cholesterol gallstone disease: focusing on the role of gallbladder

Cholecystokinin-induced satiety, a key gut servomechanism that is affected by the membrane microenvironment of this receptor

Biochemical and morphological correlations in human gallbladder with reference to membrane permeability

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