gastrins and methylamine

Secretory granules from rat antral tissue were isolated by differential centrifugation in sucrose and were confirmed as intact by electron microscopy. Gastrin release from the isolated granules was measured in response to stimulation with amino acids or their decarboxylated amine metabolites. Nine of 13 amino acids tested were ineffective at inducing gastrin release, whereas all 13 of the amine metabolites were potent stimulants of gastrin release. A pH gradient across the granule fraction membranes was estimated by acridine orange fluorescence and indicated an acidic interior. Changes in acridine orange fluorescence as an indicator of pH gradient dissipation showed that all of the amines, but only one of the amino acids, reversed acridine orange fluorescence. Ammonium chloride, similar to amines, both reversed acridine orange fluorescence and induced release of gastrin. It is concluded that amines 1) may directly stimulate gastrin granules to release their contents and 2) tend to alkalinize the gastrin granule interior. Some amino acids, in contrast, appear to directly stimulate gastrin release and do not affect the granule pH gradient.

Topics: Acridine Orange; Amines; Amino Acids; Animals; Cell Fractionation; Centrifugation, Density Gradient; Cytoplasmic Granules; Gastric Mucosa; Gastrins; Kinetics; Male; Methylamines; Microscopy, Electron; Pyloric Antrum; Rats; Rats, Inbred Strains; Spectrometry, Fluorescence

We investigated the relationship between the pH dependence of meal-stimulated gastrin release and the permeability of the antral mucosa to dietary amines. This study was undertaken after previous work from our laboratory had demonstrated that dietary amines are potent in vivo and in vitro stimulants of gastrin release and that it is well established that amines are trapped in acidic environments. Three contrasting experimental model systems were employed to investigate the association of these two pH-dependent properties. In the first in vivo study, it was demonstrated that ingestion of standard rat Chow resulted in an increase in circulating gastrin and ammonia levels, whereas the postprandial increases in both properties were abolished if the rats ingested Chow that was preacidified to a pH of 2.4. Second, the antral uptake of the fluorescent cyclic amine, quinacrine, from the gastric lumen of pylorus-ligated rats was monitored by fluorescent microscopy and spectrophotometry and was demonstrated to be inhibited in a step-wise fashion as the luminal pH was decreased. Lastly, our in vitro studies suggested that the transport of [14C]methylamine into canine antral mucosa mounted in Ussing chambers was pH-dependent, as was gastrin release into the incubation medium. Thus, all the data are consistent with the possibility that meal-stimulated gastrin release is inhibited at low pH, due (in part) to the protonation of dietary amines, preventing their diffusion into the G cell to activate hormone secretion.

Topics: Amines; Ammonia; Animals; Cimetidine; Diet; Dogs; Fasting; Gastric Mucosa; Gastrins; Hydrogen-Ion Concentration; In Vitro Techniques; Male; Methylamines; Microscopy, Fluorescence; Pyloric Antrum; Quinacrine; Rats; Rats, Inbred Strains; Spectrometry, Fluorescence