Studies on the Specificity of Pancreatic Polypeptide Binding (Including Partial Chemical Characterization of SuchSites)

哈泽尔伍德博士发现了一种假定的“新”激素， 鸡和其他脊椎动物的胰腺，暂命名为 它APP（为禽胰多肽）。 此多肽 随后已被定位在胰腺的所有 研究的脊椎动物，包括人，以及在神经 在那些没有胰腺的生物体中， （昆虫等）。 最初的研究表明了深远的影响 对碳水化合物和脂质代谢的影响 在过去的10年里， 越来越多的人意识到， 相似的PP存在于身体的不同部位。 因此，PP是 仅限于胰腺，PYY在很大程度上仅限于 大肠和结肠，和NPY似乎是丰富的 分布于大脑和周围神经系统。 最近 研究结果表明，APP对某些 胃、胰腺和肠道结构的功能。 尽管有这些积极的发现，PP作用的分子基础， 所有这些不同行动的共同点 多肽的相互作用，尚未确定。 最近哈泽尔伍德发现APP与细胞结合（相互作用）， 从鸡脑中制备的膜比用 从任何其他组织制备的膜。 这些发现表明， 大脑可能是APP作用的“靶点”。 之前 发展到APP和大脑功能的复杂性 如果不是必须的话， 尽可能多地了解这些结合位点， 这些因素改变了这些网站的数量以及能力， 结合循环APP，特别是与其他组织相关的APP 其中APP和PP已被证明具有特定的动作。 将开展研究， APP与脑和肝膜结合的要求。 从生理上操纵这些部位的尝试也将是 贯彻 最后，哈泽尔伍德计划建立 PP样分子与这些位点结合的特异性， 比较NPY、PYY和APP结合亲和力。 是 我希望对这一问题有一个批判性和有意义的理解， PP在脊椎动物中的基本作用和意义， 结果.

Dr. Hazelwood discovered a putative "new" hormone in the pancreas of chickens and other vertebrates and tentatively named it APP (for avian pancreatic polypeptide). This polypeptide subsequently has been localized in the pancreata of all vertebrates studied, including man, as well as in the nervous system in those organisms which do not possess a pancreas (insects, etc.). Original studies indicated a profound effect on carbohydrate and lipid metabolism. Within the last 10 years a growing awareness has developed that a family of structurally similar PPs reside in different parts of the body. Thus PP is restricted to the pancreas, PYY is largely restricted to the large intestine and colon, and NPY appears to be abundantly distributed in the brain and peripheral nervous system. Recent findings have indicated a powerful effect of APP on certain functions of the stomach, pancreas and intestinal structures. Despite these positive findings the molecular basis of PP action, the common denominator interrelating all of these diverse actions of the polypeptide with each other, has not been determined. Recently Hazelwood has found that APP binds (interacts) with cell membranes prepared from chicken brain more avidly than with membranes prepared from any other tissue. Such findings indicate that the brain may be a "target site" for APP action. Before progressing to the complexities of APP and functional brain processes, it is desirable- if not essential- to characterize these binding sites and to learn as much as possible about factors which alter these sites in number as well as ability to bind circulating APP particularly in relation to other tissues where a APP and PP have been shown to have specific actions. Studies will be undertaken to characterize the chemical requirements for binding APP to brain and liver membranes. Attempts to manipulate these sites physiologically also will be carried out. Finally, Hazelwood plans to establish the specificity of the binding of PP-like molecules to these sites by comparing the NPY, PYY and APP binding affinities. It is expected that a critical and meaningful understanding of the fundamental action and significance of PP in vertebrates will result.