Endogenous peptide YY and neuropeptide Y inhibit colonic ion transport, contractility and transit differentially via Y-1 and Y-2 receptors

Abstract

BACKGROUND AND PURPOSE: Peptide YY (PYY) and neuropeptide Y (NPY) activate Y receptors, targets under consideration as treatments for diarrhoea and other intestinal disorders. We investigated the gastrointestinal consequences of selective PYY or NPY ablation on mucosal ion transport, smooth muscle activity and transit using wild-type, single and double peptide knockout mice, comparing mucosal responses with those from human colon. EXPERIMENTAL APPROACH: Mucosae were pretreated with a Y₁ (BIBO3304) or Y₂ (BIIE0246) receptor antagonist and changes in short-circuit current recorded. Colonic transit and colonic migrating motor complexes (CMMCs) were assessed in vitro and upper gastrointestinal a..