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Physiological and Biochemical Studies on apelin, a novel gastrointestinal hormone from stomach

胃中新型胃肠激素apelin的生理生化研究

基本信息

批准号：
11470127
负责人：
TATEMOTO Kazuhiko
金额：
$ 8.06万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

The principal aim of this proposal is to study physiological and biochemical characterization of apelin, a novel gastrointestinal hormone isolated from the stomach. Toward this goal, a specific immunoassay for apelin has been developed, and using this assay, we found that apelin is distributed in a wide variety of tissues including the spleen, liver, mammary gland, pancreas, kidney, spinal cord, lung, stomach, brain, intestine, and heart. We also determined the molecular forms of apelin in these tissues. In the lung, kidney, intestine, and brain, a major peak of apelin was observed at a position almost identical to that of apelin-17, while, in the spleen, a major peak was detected at a position corresponding to that of apelin-36. The liver extract seemed to contain two major peptides similar to apelin-13 and apelin-17. We also studied the location of apelin in rat tissues using immunohistochemical techniques. Apelin was present in the endothelia of the small arteries of the spleen, lung, intestine, kidney, heart, pancreas, liver, and gastrointestinal tract. Apelin was also found in the white adipose tissues and the stomach wall. We examined biological activities of apelin and found that apelin lowered blood pressure in rats and also released cholecystokinin (CCK) from dispersed intestinal endocrine cells. We also found that apelin is present in milk, thus, the peptide may have a role as an exogenous CCK-releasing factor. Since apelin is a ligand for the HIV coreceptor APJ, we tested the effect of apelin on HIV infection, and found that apelin blocked the entry of HIV-1 and HIV-2. Apelin-36 more effectively blocked HIV infection than apelin-12 or apelin-13. We also found that the administration of apelin suppresses cytokine production by mouse spleen cells. These studies support the speculation that apelin may be involved in the modulation of immune responses.

本研究的主要目的是研究从胃中分离的新型胃肠激素爱帕琳的生理生化特性。为此，已经开发了针对爱帕琳的特异性免疫测定，并且使用该测定，我们发现爱帕琳分布在多种组织中，包括脾、肝、乳腺、胰腺、肾、脊髓、肺、胃、脑、肠和心脏。我们还确定了这些组织中apelin的分子形式。在肺、肾、肠和脑中，在与爱帕琳-17几乎相同的位置处观察到爱帕琳的主峰，而在脾中，在对应于爱帕琳-36的位置处检测到主峰。肝脏提取物似乎含有两种与爱帕琳-13和爱帕琳-17类似的主要肽。我们还研究了爱帕琳在大鼠组织中的位置，使用免疫组织化学技术。爱帕琳存在于脾、肺、肠、肾、心脏、胰腺、肝和胃肠道的小动脉的内皮中。在白色脂肪组织和胃壁中也发现了Apelin。我们研究了apelin的生物活性，发现apelin降低大鼠血压，并从分散的肠道内分泌细胞释放胆囊收缩素（CCK）。我们还发现，爱帕琳是存在于牛奶中，因此，肽可能有作为一个外源性CCK释放因子的作用。由于爱帕琳是HIV辅助受体APJ的配体，我们测试了爱帕琳对HIV感染的影响，发现爱帕琳阻断HIV-1和HIV-2的进入。爱帕琳-36比爱帕琳-12或爱帕琳-13更有效地阻断HIV感染。我们还发现给予爱帕琳抑制小鼠脾细胞的细胞因子产生。这些研究支持了爱帕琳可能参与免疫应答调节的推测。