Abstract

Glycine-extended gastrin enhances somatostatin release from cultured rabbit fundic D-cells

Highlights

  • Gastrin is initially synthesized as a larger precursor protein and subsequently processed, via a multi-step pathway, to the classical active carboxyl-terminal amidated peptide[1]

  • The majority of studies have examined the pathophysiological roles of gastrin precursors in gastrointestinal cancers and considerable data have implicated these peptides as stimulants of proliferation and/or inhibitors of apoptosis in a variety of tissues and cell lines, including Barrett’s oeosphagus and oesophageal adenocarcinoma[2,3], stomach[4,5], pancreas[6,7] and normal and malignant colonic epithelium[8,9,10,11,12].Growth promoting effects of G-Gly on lung cancer have been reported[13]

  • Gastrin alone did stimulate somatostatin release but was less effective than CCK and neither gastrin nor the gastrin plus G-Gly combination had any effect on CCK-stimulated gastrin release

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Summary

Introduction

Gastrin is initially synthesized as a larger precursor protein and subsequently processed, via a multi-step pathway, to the classical active carboxyl-terminal amidated peptide[1]. The precise cell signaling pathways activated by gastrinprocessing intermediates have not been definitively described, it seems in most cases that mechanisms distinct from the classical gastrin (CCK2) receptor are involved[3,6,10] It is not yet clear whether these gastrin-processing intermediates have distinct physiological, as opposed to pathophysiological roles. Glycine-extended gastrin is produced and stored in significant amounts in the gastric antrum, has gastrointestinal trophic effects and interacts with amidated gastrin to modulate gene expression and gastric acid secretion[14,15,16] Gastrin stimulates both acid secretion and somatostatin release as a feedback inhibitory mechanism[17]. The current study was designed to assess the effects of G-Gly on somatostatin release from D-cells and compare these effects with those of amidated gastrin

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