Effects of the new anti-ulcer drug ecabet sodium (TA-2711) on pepsin activity. I. Inactivation of enzyme protein.
To investigate the mechanism of the anti-peptic action of ecabet sodium (TA-2711) observed in pylorous-ligated rats, effects of this drug on the peptic activity of rat gastric juice, purified hog pepsin and pepsinogen were studied in vitro. After incubation with or without ecabet at acidic pH, the reaction mixture was centrifuged, and the peptic activity of the supernatant was measured. Ecabet depressed the peptic activity of pepsin and pepsinogen in parallel with a decrease in the protein concentration of the respective supernatant. Depression was greatest with pepsinogen (97% at 2.5 mg/ml of the drug) followed by gastric juice (about 60% at 10 mg/ml), and inhibition of the peptic activity of pepsin was weakest (about 10% at 10 mg/ml). When a fraction of the rat gastric juice containing substances with molecular weights below 10,000 was added to the pepsin solution, the anti-peptic activity of ecabet was potentiated. These results suggest that oral dosing of ecabet reduces the peptic activity of gastric juice by precipitating pepsin, which is facilitated by an unknown component(s) of gastric juice, and that the inactivation of pepsinogen may also contribute to the anti-peptic activity of ecabet.
Ito
Y
Y
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Nakamura
S
S
Onoda
Y
Y
Sugawara
Y
Y
Takaiti
O
O
D045784:Abietanes; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D005750:Gastric Juice / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D010434:Pepsin A / Q000037:antagonists & inhibitors*; D010435:Pepsinogens / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D045784:Abietanes; D000897:Anti-Ulcer Agents; D004224:Diterpenes; D010435:Pepsinogens; C061681:ecabet; D010434:Pepsin A