The effects of neuropeptide y and related pancreatic polypeptides upon gastrointestinal epithelial function

The three major members of the pancreatic polypeptide family, neuropeptide Y (NPY) peptide YY (PYY) and pancreatic polypeptide (PP), exert multiple effects upon gastrointestinal (GI) processes. One common characteristic observed in many mammalian mucosal preparations, is an inhibitory effect upon both basal and secretagogue-stimulated ion transport. Changes in vectorial electrogenic ion transport across epithelial preparations placed in modified Ussing chambers are measured continuously under voltage-clamp (at 0 mV) conditions. In rat jejunal mucosal NPY (an enteric neuropeptide) or its endocrine analogue PYY, exert antisecretory responses mediated via Y2-like receptors located on basolateral epithelial surfaces. In colonie preparations recent studies have shown that YI receptors (present on both prejunctional terminals and basolateral epithelial domains) are also involved. PP however, has little if any antisecretory action upon rat mucosal preparations but certain human adenocarcinoma cell monolayers are sensitive to basolateral application of this peptide, indicating the presence of Y4-like receptors. Human epithelial cell lines do not on the whole exhibit sensitivity to either NPY or PYY (Cox et al, unpublished observations) with two notable exceptions thus far. One cell line (Colony-6) expresses a combination of Yrreceptors and a PP-preferring population that is insensitive to the Yrselective antagonist, BIBP3226. Another cell line (Colony-1) has recently been found to express Y4-like receptors, but is not sensitive to either NPY or PYY. Colony-1 (and HT-29) are being used to stably transfect and over-express Y receptors, and these studies are providing interesting insights into the functional consequences of Y-receptor activation desensitization and cross-talk.