MULTIPLE RECEPTORS FOR THE PANCREATIC-POLYPEPTIDE (PP-FOLD) FAMILY - PHYSIOLOGICAL IMPLICATIONS

The pancreatic polypeptide (PP-fold) family of peptides consists of th e endocrine peptides, pancreatic polypeptide (PP) and peptide YY (PYY) , and the neuroneally derived peptide, neuropeptide Y (NPY), All three peptides are found in the circulation, with PP found primarily in the pancreas and PYY found principally in the gut. NPY is released into t he circulation from neuroneal stores in response to stress. These pept ides have broad peripheral actions on a number of organs. Not surprisi ngly, PYY and PP are believed to play an important role in the functio n of the gastrointestinal tract while NPY is a potent vasconstrictor a nd may have effects on the gut through the enteric nervous system, In the brain, NPY has been implicated in anxiety and depression, feeding and obesity, memory retention, neuroneal excitability, endocrine funct ion, and metabolism, Recent advances in the molecular biology of the r eceptors for these peptides have resulted in the identification of at least six receptor subtypes with varying peptide pharmacology. Compare d to other G-protein coupled receptor families, the PP-fold peptide re ceptors exhibit a relatively low level of sequence identity. Further a dvances in the development of selective agonists and antagonists for i ndividual receptor subtypes will be needed to understand further their role in physiological function.