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

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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.