Pancreatic polypeptide is an agonist of neuropeptide Y (NPY) receptors that reduces forskolin-induced cAMP accumulation in L-M(TK-) cells recombinantly expressing human and rat Y4 receptors (EC50s = 87.1 and 36.3 pM, respectively). It binds to Y1 and Y5 receptors with Ki values of 19 and 3.9 nM, respectively, for human and 50 and 2.4 nM, respectively, for rhesus monkey receptors. Pancreatic polypeptide also binds to rabbit Y1, Y2, Y4, and Y5 receptors (Kis = 0.39, 0.087, 0.79, and 0.24 nM, respectively). It induces contractile responses in isolated rat colon with EC50 values of 1.6 and 0.7 nM for ascending and descending colon segments, respectively. In vivo, pancreatic polypeptide (0.7-7 nmol, i.c.v.) increases food intake in rats.
