Altered Vasoconstrictor Responsiveness in Vitamin D-Induced Arteriosclerotic Rat Aortas

Abstract

ABSTRACT-To investigate the mechanism of the anti-peptic action of ecabet sodium (TA-2711) observed in pylorus-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 activ ity of pepsin and pepsinogen in parallel with a decrease in the protein concentration of the respective super natant. 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.

Effects of Cholesterol Loading on Autoimmune MRL-lpr/lpr Mice: Susceptibility to Hypercholesterolemia and Aortic Cholesterol Deposition

“…However, the effect on purified pepsin has been shown to be small, being less than 10010 (2). In this study, about 50010 inhibition was observed.…”

“…The previous study has suggested that ecabet exerts anti-peptic action by precipitating pepsin (2). On the other hand, the present kinetic study indicates that the peptic inhibition by ecabet might also be caused by a sub strate-inhibitor interaction.…”

“…1, 2, 3 , 4, 4a, 9,10, l Oa-octahydro-1, 4a-dimethyl-7-(l-meth ylethyl)-6-sulfo-l-phenanthrenecarboxylic acid 6-sodium salt pentahydrate), a new anti-ulcer agent, possesses anti peptic activity that was shown to result from inactivation of pepsin and pepsinogen by precipitation of these en zymes (1,2). We have observed that orally administered ecabet has a high affinity for the gastric mucosa, especial ly for necrotic areas, in rats (3,4).…”

Characteristic pathological findings and effects of ecabet sodium in rat reflux esophagitis

“…ES, a dehydroabietic acid derivative from pine resin, has been used clinically in the treatment of gastritis and gastric ulcer, and is believed to exert its effects through various mechanisms [20][21][22][23][24] . ES binds directly to the gastric mucosa, thereby protecting the mucosa against ethanol binding, and it has been shown to inhibit pepsin activity in rat and human gastric juices.…”

Bacterial activity of a new antiulcer agent, ecabet sodium, against Helicobacter pylori under acidic conditions

“…1), a new locally acting antiulcer agent, has been shown to prevent the development of various experimental ulcers and accelerate healing of chronic gastric ulcers in rats (13,14,(23)(24)(25). The mechanism of the antiulcer effect of ecabet sodium includes antipepsin activity (13,14) and enhancement of gastroduodenal mucosal defensive factors (24,25). Ecabet sodium is distributed mainly in the gastrointestinal tract, and the intestinal absorption rate is estimated to be only 3.4 to 7.0% of the dose administered in rats (11).…”