How the Magenstrasse Is Formed After Meals: Protein Aggregation Hypothesis.

Abstract

Magenstrasse (stomach road) is reported to potentially influence the absorption of orally administered drugs by facilitating a gastric emptying of ingested water under postprandial condition. We hypothesized the Magenstrasse is a consequence of the formation of protein aggregates due to the decrease in gastric pH associated with stimulated gastric acid secretion. The formation mechanism of the Magenstrasse was examined in vitro using a gastric chamber system which reproduces postprandial conditions in the stomach. Oral liquid meals containing different amounts of proteins were mixed with simulated gastric fluid containing pepsin in the gastric chamber. When a high-protein liquid meal was used, infusion of gastric acid caused protein denaturation, generating semisolid aggregates. Then, to evaluate the impact of the aggregates, fluorescein isothiocyanate-dextran 4000 (FD-4) solution was added. The presence of protein aggregates facilitated the elution of FD-4 from the gastric chamber, indicating that the semisolid aggregates suppressed mixing of FD-4 solution with meals. In addition, formation of the same type of protein aggregates was observed in vivo in rat stomach after ingesting a high-protein liquid meal. These in vitro and in vivo results support the idea that protein aggregation of liquid meals in the stomach contributes the formation of the Magenstrasse.