Gastrin receptors in the human gastrointestinal tract and pancreas

Kumamoto, Takashi; Sumii, Koji; Haruma, Ken; Tari, Akira; Tanaka, Ko; Kajiyama, Goro

doi:10.1007/bf02774183

Cited by 6 publications

(3 citation statements)

References 22 publications

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“…Gastrin is known to be an important gut‐related hormone and a growth factor for gastric cancer cells 21 , 22 and gastric tumour cells have been shown to contain its receptor. Reports have indicated that, after eradication therapy of H. pylori , a decreased level of several cytokines such as interleukin (IL)‐1, IL‐2, tumour necrosis factor‐ α and interferon‐ γ , in the gastric mucosa as well as increased acid output results in the decreased level of serum gastrin 23, 24 .…”

Section: Discussionmentioning

confidence: 99%

Morphological changes in human gastric tumours after eradication therapy of Helicobacter pylori in a short-term follow-up

Ito

Tanaka

Takata

et al. 2005

Aliment Pharmacol Ther

109

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SUMMARYBackground: It is controversial as to whether the development of gastric cancer is influenced by Helicobacter pylori eradication. If eradication itself influences the tumour morphology, this may affect the tumour discovery rate. Aim: To investigate the morphological changes in the gastric neoplasm after H. pylori eradication. Methods: We studied 37 patients with eradication therapy. After a 1-month follow-up, endoscopic re-evaluation was performed and the appearance was compared with first image. All lesions were resected endoscopically, and were subjected to histological assessment and to immunohistochemistry.

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Section: Discussionmentioning

confidence: 99%

Morphological changes in human gastric tumours after eradication therapy of Helicobacter pylori in a short-term follow-up

Ito

Tanaka

Takata

et al. 2005

Aliment Pharmacol Ther

109

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“…We have previously shown with an 125 I-labeled gastrin-binding assay that GR is present in the human gastric corpus [8]. To date, many studies have revealed the localization of GR in the human stomach.…”

Section: Introductionmentioning

confidence: 99%

Role of the Gastrin-Gastrin Receptor System in the Expansive Growth of Human Gastric Neoplasms

et al. 2008

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Background and Aim: Gastrin is one of the most important gut hormones. However, the role of the gastrin-gastrin receptor (GR) system in the growth of gastric tumors is still unclear. Methods: We examined serum gastrin levels in 957 patients with early gastric carcinoma. Next, we raised antibody against the GR and examined GR expression in 5 gastric carcinoma cell lines and 48 human gastric tumor tissues. In 28 cases, Helicobacter pylori eradication therapy was performed and morphological tumor changes were examined. Results: Serum gastrin levels were significantly higher in patients with elevated tumors than in patients with depressed tumors (p = 0.02). All gastric carcinoma cell lines expressed GR. Thirty-one of 48 (65%) gastric tumors expressed GR, and its expression was prominent in elevated-type tumor with an intestinal histologic feature. Of 28 patients who underwent eradication therapy, 9 showed gastric tumors that became flat or depressed. In these 9 cases, GR expression was detected in all tumors, and the decrease in gastrin levels was more prominent than in those without morphological change (p = 0.01). Conclusion: The gastrin-GR system plays an important role in the elevated morphology of gastric tumors.

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“…The EC 50 was 28 6 5 nM, and the K D of hG17 for the CCK-B receptor in these cells was 17 6 3.5 nM. Due to the level of receptor expression, the binding data presumably reflects the low-affinity state of the receptor as the reported highaffinity dissociation constant of 125 I-hG17 is on the order 1.6 3 10 29 M. 35 Figure 1 shows that 10 nM hG17 produces noticeable plasma membrane arrestin-GFP redistribution even after 5 min. After a 30-60 min exposure of the cells to hG17, endosomes containing arrestin-GFP become visible (compare Fig.…”

Section: Characterization Of Gastrin Binding and Signalingmentioning

confidence: 95%

G Protein-Coupled Receptor Desensitization as a Measure of Signaling: Modeling of Arrestin Recruitment to Activated CCK-B Receptors

Barak

Oakley²,

Shetzline

2003

ASSAY and Drug Development Technologies

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Gastrin is one of the principle hormonal mediators of gastric acid secretion, and its cognate receptor (CCK-B) is a member of the superfamily of GPCRs. Patients with hypergastrinemia may present with a variety of symptoms, including gastric ulcers or malignant tumors. Thus, the molecular mechanisms that terminate CCK-B receptor signaling, as well as an ability to measure gastrin bioactivity in a timely manner, have important clinical implications. In order to assess CCK-B receptor regulation, we have constructed a single cell biosensor containing the CCK-B receptor and an arrestin/GFP chimera. The gastrin biosensor responded to both immunologically detectable gastrin-17 and undetectable pentagastrin, and was able to determine the gastrin bioactivity of serum from a patient with clinical hypergastrinemia. We determined that the CCK-B receptor binds arrestin with a pharmacology mirroring CCK-B receptor signaling through inositol phosphate, and that the rate of arrestin dissociation from internalized receptor mirrors receptor recycling to the plasma membrane. Moreover, the CCK-B recycling rate is intermediate between that of Class A GPCRs such as the beta2-adrenergic receptor and Class B GPCRs such as the vasopressin type 2 receptor. Mathematical modeling of these results indicates that a common receptor conformation may underlie both CCK-B signaling and desensitization. In addition to its use in drug screening, this methodology should generalize to other receptors for use in diagnosis and monitoring of bioactive ligands involved in GPCR-based disease.

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Gastrin receptors in the human gastrointestinal tract and pancreas

Cited by 6 publications

References 22 publications

Morphological changes in human gastric tumours after eradication therapy of Helicobacter pylori in a short-term follow-up

Morphological changes in human gastric tumours after eradication therapy of Helicobacter pylori in a short-term follow-up

Role of the Gastrin-Gastrin Receptor System in the Expansive Growth of Human Gastric Neoplasms

G Protein-Coupled Receptor Desensitization as a Measure of Signaling: Modeling of Arrestin Recruitment to Activated CCK-B Receptors

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