PEPTIDE YY--COLONIC GASTRIC AND PANCREATIC INHIBITION

肽YY--结肠胃和胰腺抑制

• 批准号: 3237503
• 负责人: IAN L TAYLOR
• 金额: $ 14.78万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-06-01 至 1994-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3237503
• 关键词: aminoacid analyzer; blood chemistry; cholecystokinin; dogs; duodenum; gastric acid; gastric inhibitory peptide; gastrointestinal pharmacology; high performance liquid chromatography; hormone inhibitor; hormone metabolism; hormone receptor; hormone regulation /control mechanism; ileocolonic region; laboratory rabbit; malabsorption; miniature swine; neurotransmitters; nutrient interaction; nutrition related tag; oleate; pancreas enzyme; pancreas hormone; pancreatic juice; pancreatic polypeptide; peptide hormone; peptide hormone analog; peptide hormone metabolism; perfusion; protein sequence; radioimmunoassay; secretion; stomach /intestine bypass; stomach emptying; vagotomy; vagus nerve

Peptide YY (PYY) is released from endocrine cells in the distal gut to exert effects on upper gut function i.e., to inhibit pancreatic and exocrine secretion. Evidence exists to show that PYY may be both the "enterogastrone" and "anti-CCK' hormone described by others. PPY may also mediate the "ileal brake" phenomenon whereby gut motility is slowed in the face of malabsorption. In the present study we will extend these observations by 1) contrasting the ability of different intraluminal nutrients to inhibit acid secretion with their ability to release PYY and 2) delineating the relative importance of the large and small intestine in these phenomena. Other studies will determine if there is a role for PYY in feedback control of the pancreas. These observations in the whole animal will be extended by delineating at the cellular level, the mechanisms of PYY's release and action. We will study the role of adrenergic agonists and antagonists and peptide hormones in the release of PYY using an isolated cultured PYY cell preparation we developed. The second messenger that mediates these effects will also be delineated. In other experiments we will contrast the binding and structural characteristics of the intestinal PYY receptor with the generic NPY-PYY receptor we recently isolated and characterized in the brain. We will attempt to purify the receptor in a series of steps culminating in affinity chromatography. Other experiments will determine if the intestinal receptor is, like the central receptor, linked through an inhibitory G protein to adenyl cyclase. Finally, we will test the hypothesis that PYY acts centrally to inhibit vagal tone on the stomach. We speculate that circulating PYY is exposed to a subpopulation of central NPY-PYY receptors after it passes through the Area Postrema, an area of the blood-brain barrier that is known to be leaky. These studies should define the physiologically importance of PYY and they may delineate a unique mechanism and route of action for this gut hormone.

肽 YY (PYY) 由远端肠道的内分泌细胞释放， 对上肠道功能产生影响，即抑制胰腺和 外分泌。有证据表明 PYY 可能是 其他人描述的“肠胃素”和“抗 CCK”激素。PPY 也可能 介导“回肠制动”现象，即肠道蠕动减慢 吸收不良的脸。在本研究中，我们将扩展这些 通过 1) 对比不同管腔内的能力进行观察 通过释放 PYY 和抑制酸分泌的营养素 2）描绘大肠和小肠的相对重要性 在这些现象中。其他研究将确定是否有作用 PYY 在胰腺的反馈控制中。这些观察结果总体 动物将通过在细胞水平上描绘来扩展， PYY 的释放和作用机制。我们将研究的作用 肾上腺素能激动剂和拮抗剂以及肽激素的释放 使用我们开发的分离培养的 PYY 细胞制剂来制备 PYY。这 介导这些效应的第二信使也将被描述。 在 其他实验我们将对比结合和结构 肠道 PYY 受体与通用 NPY-PYY 的特征 我们最近在大脑中分离并表征了受体。我们将 尝试通过一系列步骤纯化受体，最终 亲和色谱法。其他实验将确定是否 肠道受体与中枢受体一样，通过 腺苷酸环化酶的抑制性G蛋白。最后，我们将测试 假设 PYY 的中枢作用是抑制胃迷走神经张力。 我们推测，循环中的 PYY 暴露于以下亚群： 中枢 NPY-PYY 受体在穿过后区（Area Postrema）后 已知有渗漏的血脑屏障区域。这些研究 应定义 PYY 的生理重要性，并且它们可能 描述这种肠道激素的独特机制和作用途径。