| Item type |
学術雑誌論文 / Journal Article_02(1) |
| 公開日 |
2007-03-22 |
| タイトル |
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タイトル |
Requirement of intact disulfide bonds in orexin-A-induced stimulation of gastric acid secretion that is mediated by OX1 receptor activation |
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言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ |
journal article |
| 著者 |
奥村, 利勝
Takeuchi, S
Motomura, W
Yamada, H
Egashira, S
Asahi, S
Kanatani, A
Ihara, M
Kohgo, Y
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| 著者 ローマ字 |
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Okumura, Toshikatsu |
| 書誌情報 |
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
巻 280,
号 4,
p. 976-981,
発行日 2001-02-01
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| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
0006-291X |
| DOI |
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関連タイプ |
isVersionOf |
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識別子タイプ |
DOI |
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関連識別子 |
10.1006/bbrc.2001.4235 |
| リンクURL |
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内容記述タイプ |
Other |
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内容記述 |
http://www.sciencedirect.com/science/journal/0006291X | http://www.sciencedirect.com/science/journal/0006291X |
| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Orexin-A is a neuropeptide consisting 33 amino acids with two intrachain disulfide bonds, namely Cys6-Cys12 and Cys7-Cys14, and is a potent stimulator of food consumption and gastric acid secretion. In contrast, orexin-B, a peptide containing 28 amino acids without disulfide bond, which has no stimulatory action of gastric acid. The objective of the present study was to characterize the receptor-mediated mechanism of orexin-A-induced stimulation of gastric acid secretion using orexin-Arelated peptides with modification of disulfide bonds. Intracisternal injection of orexin-A but not orexin-B or orexin-A (15-33) that does not contain both disulfide bonds stimulated gastric acid secretion in pylorusligated conscious rats. The ability of the stimulation of gastric acid output was less in three alanine-substituted orexin-A, [Ala^(6, 12)]orexin-A, [Ala^(7, 14)]orexin-A and [Ala^(6, 7, 12, 14)]orexin-A, than orexin-A. Orexins-induced calcium increase was measured in CHO-K1 cells expressing OX_1R or OX_2R. Orexin-A induced a transient increase in [Ca^(2+)]I in CHO-K1/OX_1R cells in a dose-dependent manner. EC_50 values for OX_1R of orexin-A, orexin-B or orexin-A (15-33) was 0.068, 0.69 or 4.1 nM, respectively, suggesting that peptides containing no disulfide bonds have lower potency for the receptor. Agonistic activity for OX1R of the three orexin-A analogues with modification of one or both disulfide bonds was significantly reduced as compared with that of orexin-A. EC_50 values for OX_2R of orexin-A and orexin-B was almost equal but potency for the receptor of orexin-A (15-33) and three alanine substituted orexin-A was less than that of orexin-A. A significant inverse relationship between gastric acid output and EC_50 values for OX_1R but not OX_2R was observed. These results suggested that the orexin-A-induced acid stimulation requires OX_1R activation and that disulfide bonds in orexin-A may have a key role in the receptor activation. |
| 注記 |
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内容記述タイプ |
Other |
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注記 |
author |
| 資源タイプ |
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内容記述タイプ |
Other |
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資源タイプ |
text |
| 著者版フラグ |
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出版タイプ |
AM |
| フォーマット |
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内容記述タイプ |
Other |
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内容記述 |
application/pdf |
| ID(XooNIps) |
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11162621 |
| 閲覧数(XooNIps) |
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| ダウンロード数(XooNIps) |
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943 |
384.pdf (230.5 kB)
