PEPTIDE YY--COLONIC GASTRIC AND PANCREATIC INHIBITION

肽YY(PYY)从远端肠道的内分泌细胞释放到 对上肠道功能有影响，即抑制胰腺和 外分泌。有证据表明，PYY可能既是 “肠胃泌素”和“抗CCK”激素被别人描述。PPY也可能 调节肠道运动减慢的“回肠制动”现象 注意力不集中的面孔。在本研究中，我们将扩展这些 观察1)对比不同管腔内的能力 营养物质通过释放PYY和PYY抑制酸分泌 2)描述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于 PYY在胰腺反馈控制中的作用。总的来说，这些观察结果 动物将通过在细胞水平上描绘， PYY的释放和作用机制。我们将研究它的作用 肾上腺素能激动剂和拮抗剂及释放中的多肽激素 使用我们开发的分离培养的PYY细胞制剂来制备PYY。这个 调解这些影响的第二信使也将被描绘出来。在……里面 其他实验我们将对比约束性和结构性 肠道PYY受体与普通NPY-PYY的特性 我们最近在大脑中分离并鉴定了受体。我们会 尝试通过一系列步骤来纯化受体，最终导致 亲和层析。其他实验将确定 肠道受体和中枢受体一样，通过一种 G蛋白对腺苷环化酶的抑制作用。最后，我们将测试 假设PYY起中枢作用，抑制胃的迷走神经张力。 我们推测，循环中的PYY接触到了 中枢NPY-PYY受体穿过最后区后， 已知有泄漏的血脑屏障区域。这些研究 应该定义PYY的生理重要性，他们可能 描绘出这种胃肠激素的独特作用机制和作用途径。

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.