Expression of progastrin-derived peptides and somatostatin in fundus and antrum of nonulcer dyspepsia subjects with and without Helicobacter pylori infection.
The hypergastrinemia and hyperacidity associated with Helicobacter pylori infection has been explained by either a primary excess of gastrin or a lack of inhibitory influence by somatostatin (SOM). The objective of the present study was to compare the concentrations of fundic and antral SOM- and antral progastrin-derived peptides in nonulcer dyspepsia (NUD) subjects with and without H. pylori infection. Antral and fundic mucosal biopsies were extracted and assayed for SOM and gastrin amide, glycine-extended gastrin (gastrin gly), progastrin, and total gastrin. There was a significant sixfold reduction in antral SOM but no change in fundic SOM content in H. pylori-infected subjects compared to uninfected subjects. Antral gastrin amide concentrations were significantly higher in infected subjects. However, the concentrations of the nonamidated gastrin forms (progastrin and glycine-extended gastrin) were significantly lower in the infected subjects, indicating an increased conversion of the precursor forms of gastrin to amidated gastrin, the type known to stimulate gastric acidity. The present study demonstrates that the elevated gastrin concentrations associated with H. pylori infection may be due to a reduction in the paracrine inhibitory effect of SOM on antral gastrin release. In addition, the posttranslational processing of gastrin to the amidated forms is increased in infected subjects, explaining why the elevation in antral gastrin is confined to the amidated form.
Zavros
Y
Y
Department of Surgery, University of Melbourne, Austin and Repatiration Medical Centre, Victoria, Australia.
Paterson
A
A
Lambert
J
J
Shulkes
A
A
D000328:Adult; D000368:Aged; D001706:Biopsy; D004415:Dyspepsia / Q000473:pathology*; D005260:Female; D005745:Gastric Acidity Determination; D005748:Gastric Fundus / Q000473:pathology*; D005753:Gastric Mucosa / Q000473:pathology; D005755:Gastrins / Q000032:analysis*; D016481:Helicobacter Infections / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000032:analysis*; D011498:Protein Precursors / Q000032:analysis*; D011706:Pyloric Antrum / Q000473:pathology*; D013004:Somatostatin / Q000032:analysis
D005755:Gastrins; D010455:Peptides; D011498:Protein Precursors; C013706:big gastrin; D013004:Somatostatin