Pharmacological Study on Analysis of Gastric Mucosal Defensive Mechanisms and Cytoprotective Action of Drugs

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Studies on gastric mucosal defensive mechanisms and their related drug action were conducted. Results obtained were as follow: 1. Drug Evaluation concerning Gastric Mucosal Defensive Functions. Gastric mucosal damage was produced by hemorrhagic shock or administration of platelet activating factor (PAF). The drug tests (prostaglandins, autonomic drugs, azulene compounds) suggest that autonomic factors and generation of superoxides are relevant to features of the former model, while vascular factors are closely involved in features of the latter model. Inflammatory responses were probably associated with PAF-induced gastric damage. Furthermore, a method for drug evaluation related to defensive mechanisms was established by measuring gastric potential difference (PD). Gastric PD was very susceptible to factors or substances damaging gastric mucosa. Using this method, the effectiveness of carbenoxolone and ammonia-induced mucosal irritation were apparently demonstrated. 2. Drug Evaluation … More concerning Gastric Blood Flow. A method for isolated perfused whole stomach preparation was established. Using this method, endothelin was found to potently and continuously produce a vaso- constriction. On the other hand, one of azulene compounds showed an increase in gastric blood flow in anesthetized rats. 3. Drug Evaluation concerning Cytoprotective Action. The release from intracellular enzymes by ethanol damaging was measured both in isolated suspended gastric mucosal cells and in gastric mucosa of anesthetized rats. Carbenoxolone exerted a cytoprotective action in the both methods. 4. Drug Evaluation concerning Gastric Mucus Secretion. A method for consecutively measuring gastric mucus secretion was established. 5. Elucidation of Neural Control in Gastric Acid Secretion. Centrally stimulating action of drugs on gastric secretion was studied. Stimulatory actions of glutamic acid related compounds were demonstrated, which would be very interesting in association with stress ulceration. 6. Drug Evaluation of Antiulcer Activities. Antiulcer activities of yeast extracts, berbeline and its related compounds, and glycyrrhetinic acid analogs were examined.In future studies, gastric mucosal defensive mechanisms will be clarified in special reference to their neural and local regulation. Less