Research Abstract |
Central nervous control systems and their signal transduction systems in gastric acid secretion were investigated in relation to appetite control and gastric ulcer therapy on the basis of pharmacology. In relation to brain-gut interaction, the effect of an appetite control substance, calcitonin was studied. A remarkable depressive effect of calcitonin on gastric secretion via central mechanisms was found. Close interaction with central serotonergic mechanisms with the action of calcitonin was confirmed similar to the inhibitory effect of morphine on gastric acid secretion. In the course of the present study, we occasionally found that a general anesthetic, pentobarbital has a strong stimulatory effect on gastric acid secretion in the urethan anesthetized rats. In the mechanism of action of pentobarbital, the important contribution of central GABA mechanism was found. In our previous study, TRH and GABA were found to stimulate gastric acid secretion which are used as the brain insufficienc
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y improver. In this connection, the effects of several drugs used for cerebral insufficiency were investigated on gastric acid secretion. Hopantenate Ca^<2+>, gamma-amino-beta-hydroxy butyrate and citicholine were found to possess distinctive stimulatory effects on gastric acid secretion. From the present results, a possibility was suggested that, in some aspect, brain metabolic state may reflect on gastric acid secretion. In relation to GABA, we investigated the effect of some glutamate agonists on gastric secretion. A remarkable stimulatory effect of kainic acid was found as well as weak effects of glutamic acid and NMDA, but not of quisqualate. These quite novel findings will stimulate further investigation in this field. We found the strong inhibitory effect of several tricyclic antidepressant related compounds on gastric acid secretion. In addition to the above mentioned results, we succeeded to device new gastric ulcer models for the brain-gut imbalance diseases. In total, our research project plan was successfully achieved. Less
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