Peptide YY: a neuroendocrine neighbor of note

Endocrine cells, enteric neurons and enterocytes provide an integrated functional defense against luminal factors, including nutrients, microbes and toxins. Prominent among intrinsic mediators is peptide YY (PYY) which is present in approximately 50% of colorectal endocrine cells and neuropeptide Y (NPY), a neurotransmitter expressed in submucous and myenteric nerves. Both peptides and their long fragments (PYY(3-36) and NPY(3-36)) are potent, long-lasting anti-secretory agents in vitro and in vivo and, they provide significant Y receptor-mediated absorptive tone in human and mouse colon mucosa. The main function of the colon is to absorb 90% of approximately 2l of daily ileal effluent (in adult humans) and Y-absorptive tone can contribute significantly to this electrolyte absorption. Blockade or loss of this mucosal Y-absorptive tone (i.e. with Y(1) or Y(2) antagonists) leads to hypersecretion and potentially to diarrhea, so Y agonists are predicted to rescue absorption by mimicking endogenous neuroendocrine PYY or neuronal NPY.