Pharmacological Studies on the Role of Excitatory Amino Acids Receptors in the Hypothalamus in the Control of Gastric Functions.

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Central nervous control of gastric acid secretion and gastric motility was studied by using perfused stomach preparations in the aneshetized rats, with special reference to the role of hypothalamic excitatory amino acid receptors. Several glutamate receptor agonists were tested for their effects on gastric acid secretion, and it was found that kinic acid markedly stimulated gastric acid secretion in the dose range of 0.1 - 10 mug/head when applied in the cerebroventriculus. Among the tested glutamate agonists, kinic acid was most potent, and NMDA was the weakest agonist. The similar tendency was observed in the effect on gastric motility. Thus, the important role of excitatory amino acids in the central control of gastric acid secretion was suggested, as well as being provided some information on the differentiation of receptor subtypes of glutamate agonists.Through related studies on the central nervous control of gastric functions, we found that the stimulation of autonomic center in the hypothalamus by 2-deoxy-D-glucose induced the typical gastric antral ulcer in combination with topical gastric application of aspirin and ammonia in the rat. It was also found that denervation of primary afferent nerves by chronic treatment in rats with capsaicin markedly aggravated the antral ulcer, suggesting the deep concern of central nervous system with gastric ulcer etiology.Besides above findings, we obtained the related new findings as follows: the stimulatory effect of pregnanolone on gastric acid secretion via central GABA receptors; biphasic influence of cholecystokinin, stimulatory and inhibitory effects, on rat gastric acid secretion through central nervous system; a new device for vagal stimulation of gastric acid secretion in the isolated mouse stomach; the important roles of C1^-/HCO_3^- exchanger in the acid production in gastric parietal cells.