Pancreatic polypeptide, peptide YY, and neuropeptide Y
- Rodger A Liddle, MD
Rodger A Liddle, MD
- Professor of Medicine
- Duke University Medical School
Originally isolated in 1968 during the preparation of insulin, pancreatic polypeptide (PP) is the founding member of the pancreatic polypeptide family [1,2]. The PP family of peptides includes peptide YY (PYY) and neuropeptide Y (NPY), which were discovered based upon their chemical structure (possessing a carboxyl-terminal tyrosine amide) [3-5]. PP, PYY, and NPY are all 36 amino acids in length, and despite structural similarities, they are found in different locations throughout the gastrointestinal tract and nervous system and possess different biological actions. PP is expressed in endocrine cells of the gut and pancreas, PYY is located in enteroendocrine cells of the ileum and colon and nerves of the enteric nervous system, and NPY is found in the central and peripheral nervous system. This wide distribution suggests that these peptides regulate many different physiological processes.
The pancreatic polypeptide (PP) peptides share a significant degree of sequence homology that produces a polyproline helix, an amphipathic alpha-helix, and an amidated carboxyl terminus, resulting in a hairpin fold known as the PP-fold (figure 1) . Although unusual for small peptides, it is believed that this tertiary structure is important for the peptides' biological activities.
Pancreatic polypeptide (PP) is secreted by specialized pancreatic islet cells (PP cells) that are distinct from those producing insulin, glucagon, or somatostatin .
Neuropeptide Y (NPY) is a principal neurotransmitter found in the central and peripheral nervous systems and is predominantly found in sympathetic neurons [8-10].
Peptide YY (PYY) has been localized to enteroendocrine cells in the mucosa of the gastrointestinal tract and is most highly concentrated in the ileum and colon . PYY is produced by two different cell types within the intestine, namely, L cells where it is colocalized with enteroglucagon and H cells of the colon and rectum. It has long been held that enteroendocrine cells are elongated or "flask"-shaped cells that reside in the intestinal mucosa with their apical surface open to the lumen of the intestine. In this position, enteroendocrine cells can "sense" luminal contents such as food or bacteria. Stimulation of cells causes the release of hormones from the basal surface into the paracellular space, where they are taken up by blood vessels and carried to distant sites of action. However, a new concept for enteroendocrine cell function is now apparent with the discovery that PYY cells possess neuropods that extend from their basal surface (figure 2) [12,13]. Neuropods contain many features typical of neurons, including synaptic boutons, neurofilaments, pre- and post-synaptic proteins, and small, clear synaptic vesicles. Moreover, it has been discovered that enteroendocrine cells connect directly with enteric nerves . This new epithelial-neural circuit provides a pathway for the gut to connect directly to the brain. It is possible that this pathway is involved in how the brain senses gut contents.
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