Altered control of gastric acid secretion in gastrin-cholecystokinin double mutant mice

Chen, Duan; Zhao, Chun Mei; Håkanson, R.; Samuelson, Linda C.; Rehfeld, Jens F.; Friis‐Hansen, Lennart

doi:10.1053/j.gastro.2003.11.012

Cited by 73 publications

(74 citation statements)

References 42 publications

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“…Over the years, it has been shown that the stomach may act as an endocrine organ (5,10,19,62) and possibly alter gastrointestinal (5, 7) and neuroendocrine (19) functions, among others. Using metabolic cages, we therefore investigated the impact of the loss of Bmpr1a in gastric epithelium on both liquid and solid metabolism in mice.…”

Section: Loss Of Gastric Epithelial Bmpr1a Leads To a Decrease In Thementioning

confidence: 99%

Epithelial BMP signaling is required for proper specification of epithelial cell lineages and gastric endocrine cells

Maloum

Allaire²,

Gagné‐Sansfaçon³

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Perreault N. Epithelial BMP signaling is required for proper specification of epithelial cell lineages and gastric endocrine cells. Am J Physiol Gastrointest Liver Physiol 300: G1065-G1079, 2011. First published March 17, 2011 doi:10.1152/ajpgi.00176.2010.-Bone morphogenetic protein (BMP) signaling within the gastrointestinal tract is complex. BMP ligands and their receptors are expressed in both epithelial and mesenchymal compartments, suggesting bidirectional signaling between these two entities. Despite an increasing interest in BMP signaling in gut physiology and pathologies, the distinct contribution of BMP signaling in the epithelium vs. the mesenchyme in gastrointestinal homeostasis remains to be established. We aimed to investigate the role of epithelial BMP signaling in gastric organogenesis, gland morphogenesis, and maintenance of epithelial cell functions. Using the Cre/loxP system, we generated a mouse model with an early deletion during development of BMP receptor 1A (Bmpr1a) exclusively in the foregut endoderm. Bmpr1a⌬GEC mice showed no severe abnormalities in gastric organogenesis, gland epithelial proliferation, or morphogenesis, suggesting only a minor role for epithelial BMP signaling in these processes. However, early loss of BMP signaling in foregut endoderm did impact on gastric patterning, leading to an anteriorization of the stomach. In addition, numbers of parietal cells were reduced in Bmpr1a ⌬GEC mice. Epithelial BMP deletion significantly increased the numbers of chromogranin A-, ghrelin-, somatostatin-, gastrin-, and serotonin-expressing gastric endocrine cells. Cancer never developed in young adult (Ͻ100 days) Bmpr1a-inactivated mice although a marker of spasmolytic polypeptide-expressing metaplasia was upregulated. Using this model, we have uncovered that BMP signaling negatively regulates the proliferation and commitment of endocrine precursor cells. Our data also indicate that loss of BMP signaling in epithelial gastric cells alone is not sufficient to induce gastric neoplasia. bone morphogenetic protein; gastric cell lineages; spasmolytic polypeptide-expressing metaplasia

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Section: Loss Of Gastric Epithelial Bmpr1a Leads To a Decrease In Thementioning

confidence: 99%

Epithelial BMP signaling is required for proper specification of epithelial cell lineages and gastric endocrine cells

Maloum

Allaire²,

Gagné‐Sansfaçon³

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Regulation of gastric acid secretion is along with histamine and gastrin. In gastrin/CCK knockout mice, studies revealed that circulating CCK is a potent acid inhibitor which stimulates somatostatin release from the fundic D cells via CCK 1 receptors which in turn inhibits acid secretion from the parietal cells [30] .…”

Section: Stomachmentioning

confidence: 99%

CCK<sub>1</sub> Antagonists: Are They Ready for Clinical Use?

Peter

D’Amato²,

Beglinger

2006

Dig Dis

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Cholecystokinin (CCK) is a peptide hormone which is found both in the gastrointestinal tract throughout the human small intestine and nerves in the myenteric plexus of the enteric nervous system and in the central nervous system. This dual location constitutes the anatomical basis for this in functions as a hormone and a neurotransmitter implicated in the regulation of both systems. CCK regulates not only motor functions in the gastrointestinal tract like lower oesophageal sphincter relaxation, gastric secretion and emptying, gall bladder contractility and bile secretion into the duodenum, intestinal and colonic motility, but also sensory functions and plays a role in the regulation of food intake. These effects are mediated through selective receptors CCK₁ and CCK₂. Over the last few years, research has focused on understanding the role of CCK, its receptors with antagonists at the biological, pharmacological, clinical and therapeutic level. As far as the CCK₁ antagonists is concerned, important inroads have been made in the potential role of these antagonists in the treatment of GERD, IBS and pancreatitis. They have also shown encouraging results in sphincter of Oddi dysfunction and some gastrointestinal cancers. This review focuses on the recent ad vances of the biological role of CCK and their CCK₁ antagonists: their current basic and clinical status in gastroenterology, with particular emphasis on the potential therapeutic role of the CCK₁ antagonists and future research directions.

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“…More recently, genetic models lacking CCK or its receptors have become available. Work with these models has further validated feeding inhibitory actions for peripheral CCK and provided systems for evaluating how defects in a satiety pathway interact with overall metabolic controls (Chen et al, 2004;Kopin et al, 1999;Miyasaka et al, 2002). In this review, we will focus on the Otsuka Long Evans Tokushima Fatty (OLETF) rat that lacks the CCK1 receptor.…”

Section: Introductionmentioning

confidence: 99%

Hyperphagia and obesity of OLETF rats lacking CCK1 receptors: Developmental aspects

Moran

2006

Dev. Psychobiol.

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Otsuka Long Evans Tokushima Fatty (OLETF) rats have a deletion in the gene encoding the cholecystokinin-1 (CCK1) receptor. This deletion prevents protein expression, making the OLETF rat a CCK1 receptor knockout model. Consistent with the absence of CCK1 receptors, OLETF rats do not reduce their food intake in response to exogenously administered CCK and consume larger than normal meals. This deficit in within-meal feedback signaling is evident in liquid as well as solid meals. Neonatal OLETF rats show similar differences in independent ingestion tests. Intake is higher and is reflected in greater licking behavior. Neonatal OLETF rats also have diminished latencies to consume and higher initial ingestion rats. Adult OLETF rats are hyperphagic and obese. Although arcuate nucleus peptide gene expression is apparently normal in OLETF rats, when obesity is prevented through pair-feeding to amounts consumed by control Long Evans Tokushima Otsuka (LETO) rats, dorsomedial hypothalamic NPY mRNA expression is significantly elevated in OLETF rats. NPY overexpression is also evident in preobese, juvenile OLETF rats suggesting a causal role for this overexpression in the hyperphagia and obesity. Running wheel exercise normalizes food intake and body weight in OLETF rats. When access to exercise is provided at a time when OLETF rats are obese, the effects are limited to the period of exercise. When running wheel access is available to younger, preobese OLETF rats, exercise results in long lasting reductions in food intake and body weight and improved glucose regulation. These lasting metabolic effects of exercise may be secondary to an exercise induced reduction in DMH NPY mRNA expression.

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Altered control of gastric acid secretion in gastrin-cholecystokinin double mutant mice

Cited by 73 publications

References 42 publications

Epithelial BMP signaling is required for proper specification of epithelial cell lineages and gastric endocrine cells

Epithelial BMP signaling is required for proper specification of epithelial cell lineages and gastric endocrine cells

CCK<sub>1</sub> Antagonists: Are They Ready for Clinical Use?

Hyperphagia and obesity of OLETF rats lacking CCK1 receptors: Developmental aspects

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