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-Effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711), a new anti-ulcer agent, on gastric secretion and experimental ulcers were investigated in rats. Oral administration of TA-2711 at doses of 25 to 100 mg/kg immediately after pyloric ligation markedly reduced pepsin activity and slightly lowered acid concentration without affecting the volume of gastric juice. Addition of TA-2711 (0.25-16 mg/ml) directly to gastric juice also reduced pepsin activity in vitro. Oral TA-2711 dose-relatedly inhibited the formation of pylorus-ligated ulcers (50-200 mg/kg), aspirin-induced gastric erosions (25-100 mg/kg) and cysteamine-induced duodenal ulcers (100-800 mg/kg). In addition, this drug prevented both the formation of gastric lesions (6.3-100 mg/kg, p.o.) and the fall in gastric potential difference (100 mg/kg, p.o.) induced by ethanol. The preventive effect against ethanol-induced lesions was suppressed by pretreatment with indomethacin (10 mg/kg, s.c.). Intravenous dosing of TA-2711 (10-100 mg/kg) never produced such effects on ethanol-induced lesions and pepsin activity as observed by oral administration. These results indicate that TA-2711 exerts its anti-ulcer effect by a local action, and it is suggested that both reduction of pepsin activity and a mucosal prostaglandin-mediated process are involved in the anti-ulcer action of TA-271 1.

The effects of rapid cooling on the mechanical and electrical activities of the guinea pig taenia coli and circular muscle of the stomach were investigated. Lowering the temperature from 32°to 10 0 C (cold shock) depolarized the membrane and increased the membrane resistance in both tissues. However, in the taenia coli, an initial reduction of membrane resistance was observed. In both tissues, contracture evoked by cold shock and rapid relaxation after rewarming, preceded the changes of membrane properties. Displacements of the membrane potential did not modify the amplitude of contracture under cold shock. Caffeine and thymol modified the membrane properties, but the effects of cold shock were still observed. The effects of cold shock were also observed on K-induced contracture. It was postulated that at least two different sites of sequestered bound Ca are located in these smooth muscles and are responsible for evoking the mechanical response. One component possesses a close relation to membrane and the other component is presumably sequestered within the muscle.

SUMMARYThe effects of low temperature (36-10o C) on the electrical properties of smooth muscle cells of the urinary bladder were investigated with microelectrodes and the double sucrose gap method.

1) Properties of the slow potential changes recorded from antral and pyloric regions of the guinea pig stomach were investigated with both the double sucrose gap and microelectrode methods. 2) Frequency, amplitude, and duration of the slow potential changes varied from 2 to 5 per min, 0 to 30 mV, and 6 to 14 sec. 3) During the slow potentials, membrane resistance was reduced. This reduction exceeded that caused by the rectifying property of the membrane. 4) The amplitude of the slow potential was enhanced by application of weak inward current pulses and decreased during weak outward current pulses. 5) The frequency of the slow potential changes was a function of the temperature. The Q10 value was 3.2. 6) Na-deficient (1/10 Na) Krebs solution suppressed the slow potential changes, but they were restored by conditioning hyperpolarization of the membrane. However, in Na-free solution the slow potential changes were generated with neither normal nor hyperpolarized membrane. 7) In low K-and low Ca-Krebs solutions, the amplitude and frequency of the slow potential changes were reduced. 8) When Cl ion was replaced by the less permeable C5H5SO3 ion, the slow potential change was abolished completely. When. Cl ion was substituted with Br ion, the frequency of the slow potential was not reduced, and in some preparations it was increased. 9) Ba ion in the presence of Ca ion increased the frequency of the slow potential changes, but in the absence of Ca ion the frequency was not increased. Sr ion could not be substituted for Ca ion in the generation of the slow potential changes.