1 Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) differentially activate three Y receptors (Y 1 , Y 2 and Y 4 ) in mouse and human isolated colon. 2 The aim of this study was to characterise Y 2 receptor-mediated responses in colon mucosa and longitudinal smooth muscle preparations from wild type (Y 2 þ / þ ) and knockout (Y 2 À/À) mice and to compare the former with human mucosal Y agonist responses. Inhibition of mucosal short-circuit current and increases in muscle tone were monitored in colonic tissues from