Bovine α-Lactalbumin Stimulates Mucus Metabolism in Gastric Mucosa

Abstract 

Bovine α-lactalbumin (α-LA), a major milk protein, exerts strong gastroprotective activity against rat experimental gastric ulcers induced by ethanol or stress. To elucidate the mechanisms underlying this activity, the influence of α-LA on gastric mucus metabolism was investigated in vitro and in vivo. For the in vitro study, RGM1 cells (a rat gastric epithelial cell line) were selected for observation of the direct activity of α-LA on gastric mucosal cells and cultured in the presence of either α-LA or ovalbumin (OVA), a reference protein showing no gastroprotective activity. Amounts of synthesized and secreted mucin, a major component of mucus, were determined using [³H]glucosamine as a tracer, and prostaglandin E₂ (PGE₂) levels in the culture medium were determined by RIA. For the in vivo study, the thickness of the mucus gel layer, a protective barrier for gastric mucosa, was evaluated histochemically in rat gastric mucosa. α-Lactalbumin (3 mg/mL) significantly stimulated mucin synthesis and secretion in RGM1 cells and also increased PGE₂ levels in the culture medium. In contrast, OVA showed no enhancing effects under identical conditions. Neither indomethacin, a cyclo-oxygenase inhibitor, nor AH23848, a prostaglandin EP4 receptor antagonist, affected α-LA-induced enhancement of mucin synthesis and secretion. In vivo, oral administration of α-LA (300 mg/kg×3 times/d×7 d) increased the thickness of the mucus gel layer in rats. These results indicate that α-LA fortifies the mucus gel layer by stimulating mucin production and secretion in gastric mucus-producing cells, and that this enhancing effect is independent of endogenous PGE₂. Comparison of the efficacy of α-LA with OVA suggests that the activities observed in RGM1 cells are closely related to the gastroprotective effects in rat gastric ulcer models. In conclusion, α-LA stimulates mucus metabolism, and this action may be responsible for its gastroprotective activity.

Key words: α-lactalbumin, mucus, prostaglandin, gastroprotective activity