| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1988: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1987: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
Fluctuations of the gastric mucosal defensive ability during acid sercetory states were investigated in rats using histamine (Hi) as a stimulator of acid secretion. Hi (3-20 mg/kg,s.c.) at the doses which caused stimulation of acid secretion protected the gastric mucosa against 0.6 N HCl-induced gastric lesions, inhibited gastric motility, and increased alkaline secretion in the stomach but not in the duodenum. These actions of Hi were significantly attenuated by both cimetidine, an H2 antagonist, and indomethacin, a cyclooxygenase inhibitor, suggesting involvement of H2-receptors and endogenous prostaglandins (PGs). On the other hand, a single dose treatment of Hi (40-80 mg/kg) markedly enhanced the mucosal microvascular permeability of the stomach in the presence of high doses of 16,16-dimethyl PGE2 (dmPGE2: 10-30 ug/kg), resulting in hemorrhagic mucosal injury, and the repeated teatment with these two agents for 4 days produced severe lesions in the gastric mucosa. hi (20 mg/kg) also had a deleterious influence on the pre-existing lesions in the gastric mucosa and significantly delayed the healing of 0.6 N HCl-induced lesions. These data, all together, suggest that the mucosal defensive ability may be increased during acid stimulatory states, by the mechanisms mediated with endogenous PGs through H2 receptors in addition to those directly associated with the process of acid secretion. Hi by itself may not be an ulcerogenic substance and may be involved in the regulatory mechanism of the mucosal homeostasis in the stomach, in collaboration with endogenous PGs; they work together and antagonize each other, depending upon the situations.
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