Study of Receptor Binding and Growth Effect of Gastrin Gene Products
type: CreativeWork
description: Colorectal cancer is the third leading cancer in US, accounted for 160,000 cases and 57,000 deaths per year. Gastrin (G17) has been postulated as a growth factor for colorectal cancer development. Gastrin, a heptadecapeptide, is a gut hormone produced by the G cells in the gastric antrum and functions primarily in stimulating acid secretion from the parietal cells. Besides its role as an acid secretagogue in the stomach, gastrin has also been reported to act as growth factor for both normal and malignant cells. Various reports have shown the trophic effect of gastrin gene products on carcinoma cells, especially colonic cancer cells. The C-terminal tetrapeptide of gastrin, shared with Cholecystokinin (CCK), is the minimal sequence required for its biological effect through the CCK2 receptor. Structure-functional studies of gastrin and the CCK2 receptor revealed the importance of Phe in residue 17 of gastrin in receptor recognition. Removal of Phe" abolishes the binding of gastrin to the human CCK2 receptor but leads to an antagonist for the rat CCK2 receptor-mediated acid secretagogue effect of gastrin. Hence, interspecies differences bring some concerns on the application of animal models in studying the interaction of peptides with the human receptor. Gastrin heptapeptide, G(ll-17), which has been shown to have a high affinity for the human CCK2 receptor with similar affinity to G17, is used as the basic peptide for the study. To determine what characteristic of gastrin residues are important for the binding to the CCK2 receptor, several gastrin analogs were tested, which include: (i) para-substituted analogs, [Leu15,p-X-Phe17]G(ll-17), where X=C1, CH3, and NH2, (ii) analogs in which Phe" was substituted with hydrophobic amino acids of increasing size, Ala, Abu, Val, Leu and Cha and (iii) analogs in which Phe" was replaced by another aromatic amino acid, Trp. Using [^H-propionyl]CCK8, the affinity of gastrin analogs for the human CCK2 receptor was analyzed by compe…
abstract: Colorectal cancer is the third leading cancer in US, accounted for 160,000 cases and 57,000 deaths per year. Gastrin (G17) has been postulated as a growth factor for colorectal cancer development. Gastrin, a heptadecapeptide, is a gut hormone produced by the G cells in the gastric antrum and functions primarily in stimulating acid secretion from the parietal cells. Besides its role as an acid secretagogue in the stomach, gastrin has also been reported to act as growth factor for both normal and malignant cells. Various reports have shown the trophic effect of gastrin gene products on carcinoma cells, especially colonic cancer cells. The C-terminal tetrapeptide of gastrin, shared with Cholecystokinin (CCK), is the minimal sequence required for its biological effect through the CCK2 receptor. Structure-functional studies of gastrin and the CCK2 receptor revealed the importance of Phe in residue 17 of gastrin in receptor recognition. Removal of Phe" abolishes the binding of gastrin to the human CCK2 receptor but leads to an antagonist for the rat CCK2 receptor-mediated acid secretagogue effect of gastrin. Hence, interspecies differences bring some concerns on the application of animal models in studying the interaction of peptides with the human receptor. Gastrin heptapeptide, G(ll-17), which has been shown to have a high affinity for the human CCK2 receptor with similar affinity to G17, is used as the basic peptide for the study. To determine what characteristic of gastrin residues are important for the binding to the CCK2 receptor, several gastrin analogs were tested, which include: (i) para-substituted analogs, [Leu15,p-X-Phe17]G(ll-17), where X=C1, CH3, and NH2, (ii) analogs in which Phe" was substituted with hydrophobic amino acids of increasing size, Ala, Abu, Val, Leu and Cha and (iii) analogs in which Phe" was replaced by another aromatic amino acid, Trp. Using [^H-propionyl]CCK8, the affinity of gastrin analogs for the human CCK2 receptor was analyzed by compe…
author: Wibowo, Felicitas I.
language: en_US
date published: 2002
date modified: 2026-07-24T01:51:30Z
provider: Creighton University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Creighton University

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property ID: Handle
value: http://hdl.handle.net/10504/68508