1999 Fiscal Year Final Research Report Summary
CHARACTERIZATION OF GASTRIC ACID SECRATION BASED ON THE STUDY OF HISTAMINE H2 RECEPTOR AND HELICOBACTER PYROLI
| Project/Area Number |
10670512
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | DEPARTMENT OF INTERNAL MEDICINE TOKYO WOMEN'S UNIVERSITY OF SCHOOL OF MEDICINE DAINI HOSPITAL |
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Principal Investigator |
SAITO Toshihito TOKYO WOMEN'S UNIVERSITY MEDICAL UNIVERSITY ASSIST. PROF., 医学部・内科, 講師 (50246609)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI haruki TOKYO WOMEN'S MEDICAL UNIVERSITY ASSIST, 医学部・内科, 講師 (00246612)
HIRAKAWA Junko TOKYO WOMEN'S MEDICAL UNIVERSITY ASSIST, 医学部・内科, 助手 (40266854)
OTUKA Hiroko TOKYO WOMEN'S MEDICAL UNIVERSITY ASSIST. PROF., 医学部・内科, 助手 (20307606)
FUKUSHIMA Yasushi UNIVERSITY OF TOKYO RESIDENT, 医学部・内科, 医員
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| Project Period (FY) |
1998 – 1999
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| Keywords | HISTAMINE H2 RECEPTOR / LOCALIZATION / IMMUNOHISTOCHEMISTRY / H2 RECEPTOR ANTAGONIST / HELICOBACTER PYROLI / N-ALFA-METHYLHISTAMINE / H2受容体結合 / ヒスタミンH2受容体 |
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| Research Abstract |
The histamine H2 receptor (H2R) is a target for major anti-ulcer drugs. H2 antagonists have been widely used for the treatment of peptic ulcer disorders since their discovery in the 1970s. The H2R was assumed to reside in gastric parietal cells and to be involved in gastric acid production via production of cyclic adenosine monophosphate (cAMP), although no direct evidence of pariental cells have been presented to date. In this study, we cloned the mouse H2R gene and generated a specific antibody, we immunohistochemically investigated gastric and subcellular localization of H2R. Next, we expressed human H2 receptor (HH2R) in Chinese hamster ovary cells (CHO) and directly investigated the effects of various H2 receptor antagonists. IT-066 inhibited ィイD13ィエD1H tiotidine binding and histamine stimulated cAMP production more potently than famotidine and ranitidine. In addition, preincubation of IT-066 marked inhibtory effects long after extensive washing. Paraformaldehyde fixation of cells blunted inhibition of ィイD13ィエD1H tiotidine binding induced by preincubation with IT-066, but not that by preincubation with famotidine or ranitidine. IT-066 has potent and long-lasting antagonisms on HH2R. At least one of the IT-066 binding sites is not shared by famotidine, ranitidine, or tiotidine and it affected by paraformaldehyde. Using HH2R expressed CHO, we also analyzed the effect of N-alfa-methylhistamine (NMeH) on cAMP production. NMeH is an H2 receptor agonist and produced by H.pyroli in gastric mucosa. NMeH was more potent in terms of cAMP production than histamine. Although NMeH inhibit acid secration via H3 receptor, it may stimultanously stimulate acid secration via H2 receptor.
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