Amino acids and amines stimulate gastrin release from canine antral G-cells via different pathways.

Abstract

The major determinant of meal-stimulated gastric acid secretion is the antral hormone gastrin. Decarboxylated amine derivatives of amino acids have been proposed as the final common mediators of gastrin secretion stimulated by a meal. We explored the cellular basis for this hypothesis using a recently developed isolated canine 0-cell model. Both amino acids and, more potently, their corresponding amines, directly stimulated gastrin release. Amino acid-stimulated gastrin secretion was unaffected by decarboxylase inhibitors (alpha methyldopa, aminooxyacetic acid, and 4-deoxypyridoxine) but enhanced by bombesin, isobutylmethylxanthine, and dibutyryl cAMP. Somatostatin inhibited amino acid-stimulated gastrin release via a pertussis toxin-sensitive GTP-binding protein.

EGF receptor activation stimulates endogenous gastrin gene expression in canine G cells and human gastric cell cultures.

“…Total RNA was prepared 16 h after the administration of agonist. The resulting antral G cell cultures were a mixed population of epithelial cells and fibroblasts of which 15-25% were G cells by immunohistochemistry (2). The concentrations of agonists used here have been shown to maximally stimulate gastrin release or promoter activity (3,19).…”

“…Primary canine G cell cultures were prepared by the Michigan Gastrointestinal Peptide Center using collagenase digestion and counterflow elutriation as described previously (2,3). Approximately 6-8 ϫ 10 6 cells were plated onto 100-mm culture dishes precoated with Matrigel (Collaborative Research Inc., Lexington/Waltham, MA) in Dulbecco's MEM (GIBCO BRL, Gaithersburg, MD) containing 10% dog serum, 100 g/ml penicillin, and 100 g/ml streptomycin in a humidified atmosphere of 5% CO 2 and 95% air.…”

“…Gastrin release is regulated by changes in gastric pH, cAMP, phorbol esters, bombesin, and amino acids (1)(2)(3)(4). Proton pump inhibitors stimulate gastrin gene expression by inhibiting gastric acid secretion and by raising gastric pH (5,6).…”

Amine precursor uptake and decarboxylation: significance for processing of the rat gastrin precursor

“…The present data raise the idea that modulation of secretory granule amine content, via protonamine exchange, provides a mechanism for selective control of prohormone cleavage. In this context, it is worth noting that dietary amines have already been shown to influence other aspects of G-cell function (Lichtenberger, Delansorne & Graziani, 1982;Delvalle & Yamada, 1990;Dial, Cooper & Lichtenberger, 1991). Several amines including phenylethylamine and tyramine have been shown to be more potent gastrin releasers than their corresponding amino acids; moreover, there is also evidence that amine-induced increases in intragranular pH promote gastrin release (Lichtenberger et al 1982;Delvalle & Yamada, 1990).…”

“…In this context, it is worth noting that dietary amines have already been shown to influence other aspects of G-cell function (Lichtenberger, Delansorne & Graziani, 1982;Delvalle & Yamada, 1990;Dial, Cooper & Lichtenberger, 1991). Several amines including phenylethylamine and tyramine have been shown to be more potent gastrin releasers than their corresponding amino acids; moreover, there is also evidence that amine-induced increases in intragranular pH promote gastrin release (Lichtenberger et al 1982;Delvalle & Yamada, 1990). It seems possible, then, that dietary amines might modulate both the post-translational processing of progastrin and the secretion of these peptides, thereby providing the capacity to match the secretory products of the G-cell with particular stimuli in the gastric lumen.…”