The colonic prokinetic activity of a newly synthesized compound,

No abstract

Abstract-Effectsof TA-2711 on gastric mucosal lesions induced by various necrotizing agents and several defensive factors of gastric mucosa were investigated in rats. Oral administration of TA-2711 at 12.5 to 200 mg/kg prevented the formation of gastric mucosal lesions induced by 99.5% ethanol, 0.6 N HCI, 0.2 N NaOH and boiling water with ED50 values of 24, 58, 16 and 101 mg/kg, respectively. Oral TA-2711 at 100 mg/kg increased the gastric mucosal prostaglandin E2 (PGE2) level without any change in transmucosal potential difference. A sustained decrease in gastric mucosal blood flow produced by intragastric administration of 99.5% ethanol was inhibited by oral TA-2711 (50, 100 mg/kg) and 16,16-dimethyl PGE2 (10 ucg/kg). The effect of TA-2711 on ethanol-induced decrease in blood flow was suppressed by indomethacin (10 mg/kg, s.c.). Oral TA-2711 (25-100 mg/kg) dose-dependently increased the amount of mucus adherent to the gastric mucosa.In addition, gastric HCO3 secretion was increased by intragastric TA 2711 at 2.5 and 5.0 mg/ml.These results suggest that TA-2711 enhances gastric mucosal resistance by increasing mucus and HCO3 secretion and by maintaining mucosal blood flow, and protects the gastric mucosa against various irritants. The effects of TA-271 1 appear to be mediated by mucosal prostaglandins such as PGE2.

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.

SUMMARY1. The effect of ouabain on the noradrenaline output from peripheral adrenergic neurones has been studied using isolated guinea-pig vasa deferentia.2. Exposure to ouabain (10-4 M) causes a gradual increase in the noradrenaline output. The effect occurs after a delay of 20 min and reaches a maximum during the period from 40-60 min.3. In the absence of external Ca, exposure to ouabain fails to produce an increase in the noradrenaline output. However, the reintroduction of Ca (2.5 mM) after a 1 hr exposure to ouabain in Ca-free media causes a rapid rise in noradrenaline output which reaches a maximum within the first 20 min. 4. After a 1 hr exposure to a low concentration of ouabain (10-5 m) the reintroduction of Ca is almost ineffective in increasing the noradrenaline output. When the concentration of ouabain is increased, the reintroduction of Ca becomes effective and causes a maximum effect with 10-4 M ouabain. In the presence of a constant amount of ouabain (10-4 M) the noradrenaline output induced by the reintroduction of Ca increases over the range 0-2-2-5 mM.5. In the presence of ouabain (10-4 M) the Ca-induced noradrenaline output increases in a linear fashion with increasing Na concentrations from 25 to 143 mm, as long as NaCl is replaced with equimolar choline chloride or isotonic sucrose.6. In the presence of the lowest effective concentration of sodium (25 mM) the noradrenaline output induced by the reintroduction of Ca after a 1 hr exposure to ouabain is potentiated by LiCl. However, in the complete absence of Na+ ions, there is no Li-dependent increase in the Ca-induced noradrenaline output.7. It is suggested that ouabain may cause an increase in noradrenaline output by an effect on the Na-dependent Ca influx system.