|Budget Amount *help
¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1999 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1998 : ¥2,200,000 (Direct Cost : ¥2,200,000)
The theme of the present project has been focused on histamine release mechanism from ECL cells via guanylate cyclase. The results are summarized in the following six point :
1) Nitric oxide (NO) donors stimulated gastric acid secretion in the mouse isolated stomach preparation. The response to their low doses, but not to their high doses, was inhibited by famotidine. The NO donors produced histamine release from ECL cells. However, these drugs inhibited gastric acid secretion probably by a direct action on gastric parietal cells.
2) Acid secretory responses to cholinergic agents and gastrin like peptides were inhibited by treatment with NOS inhibitors. Therefore, histamine release from ECL cells by NO may be involved in these acid secretory responses.
3) Membrane permeable cAMP and cGMP produced histamine release from ECL cells. This finding suggests that guanylate cyclase, as well as adenylate cyclase, is associated with intracellular signaling of histamine release.
4) IBMX, a nonspecific phophodiesterase inhibitor, stimulated acid secretion, but zaprinast, a V-typed phosphodiesterase inhibitor, had no effect on acid secretion. V-typed phosphodiesterase may not play a significant role in histamine release from ECL cells.
5) Treatment with drugs which increase intracellular calcium concentration stimulated acid secretion. The weak secretory response was inhibited by famotidine, but the strong response was not blocked. This finding suggests that ECL cells have higher sensitivity to intracellular calcium concentration than parietal cells.
6) Both of endogenous NO and exogenous NO inhibited histamine release from ECL cells in mast cells. Mast cells was apparently different from ECL cells in histamine releasing mechanism.