Pancreatic polypeptide and peptide YY3-36 induce Ca2+ signaling in nodose ganglion neurons

Peripheral injection of pancreatic polypeptide (PP) and peptide YY3-36 (PYY3-36), the hormones released in response to meals, reduce food intake, in which the rank order of the potency is PP > PYY3-36. These anorectic effects are abolished in abdominal vagotomized rats, suggesting that PP and PYY3-36 induce anorexia via vagal afferent nerves. However, it is not clear whether PP and PYY3-36 directly act on vagal afferent neurons. In this study, we examined the effects of PP and PYY3-36 on cytosolic Ca2+ concentration ([Ca2+](i)) in isolated nodose ganglion neurons of the mouse vagal afferent nerves. At 10(-11) M, PP but not PYY3-36 recruited a significant population of nodose ganglion neurons into [Ca2+](i) increases. PP at 10(-11) to 10(-7) and PYY3-36 at 10(-10) to 10(-7) M increased [Ca2+](i) in a concentration-dependent manner. At submaximal to maximal concentrations of 10(-10) and 10(-8) M, PP increased [Ca2+](i) in approximately twice greater population of nodose ganglion neurons than PYY3-36. Furthermore, the majority of PP-responsive neurons also exhibited [Ca2+](i) responses to cholecystokinin-8, a hormone known to induce satiety through activating nodose ganglion neurons. The results demonstrate that PP and PYY3-36 directly activate nodose ganglion neurons and suggest that the marked effect of PP on cholecystokinin-8-responsive nodose ganglion neurons could be linked to the regulation of feeding. (C) 2012 Elsevier Ltd. All rights reserved.