Neuropeptide Y and peptide YY: major modulators of gastrointestinal blood flow and function

Abstract

The present paper reviews the chemistry, distribution, and release of neuropeptide Y (NPY) and peptide YY (PYY) and evaluates their role as neuronal and hormonal regulators in gastrointestinal physiology. In addition, the current concepts of receptors for NPY and PYY, the Y1 and Y2 receptor subtypes and their localization, characterization by ligand binding studies, and structural analysis by affinity-labeling experiments, are presented and discussed. NPY is present in both central and peripheral neurons, whereas PYY is mainly expressed in endocrine cells in the lower bowel. PYY and NPY inhibit gut motility, gastric emptying and acid secretion, and pancreatic exocrine secretion and are potent vasoconstrictors in many vascular beds. It is suggested that these peptides regulate gastrointestinal function by effects on blood flow, by modulating neural control mechanism, and in some cases by direct effects on differential functional cells such as enterocytes. Multiple receptors for NPY and PYY probably exist, and these appear to fall into Y1 and Y2 types by their specificity for a long COOH-terminal fragment, NPY-(13-36) and an NPY analogue, [Leu31,Pro34]NPY. The latter is specific for Y1 receptors, whereas the COOH-terminal fragment preferentially binds to Y2 receptors. Furthermore, affinity-labeling experiments have shown that the Y1 and Y2 receptors are structurally distinct glycoproteins. It is concluded that the herein characterized Y1 and Y2 receptors may be the structural proteins that mediate the physiological actions of NPY and PYY.