Verschueren S, Janssen P, Van Oudenhove L, Hultin L, Tack J. Effect of pancreatic polypeptide on gastric accommodation and gastric emptying in conscious rats. Am J Physiol Gastrointest Liver Physiol 307: G122-G128, 2014. First published April 17, 2014 doi:10.1152/ajpgi.00043.2014 is an anorexigenic hormone released from pancreatic F cells upon food intake. We aimed to determine the effect of PP on gastric accommodation and gastric emptying in conscious Wistar HAN rats to investigate whether effects on motor function could contribute to its anorexigenic effects. Intragastric pressure (IGP) was measured through a chronically implanted gastric fistula during the infusion of a nutrient meal (Nutridrink; 0.5 ml/min). Rats were treated with PP (0, 33 and 100 pmol·kg Ϫ1 ·min Ϫ1 ) in combination with N G -nitro-L-arginine methyl ester (L-NAME; 180 mg·kg Ϫ1 ·h Ϫ1 ), atropine (3 mg·kg Ϫ1 ·h Ϫ1 ), or vehicle. Furthermore, the effect of PP was tested after subdiaphragmal vagotomy of the stomach. Gastric emptying of a noncaloric and a caloric meal after treatment with 100 pmol·kg Ϫ1 ·min Ϫ1 PP or vehicle was compared using X-rays. PP significantly increased IGP during nutrient infusion compared with vehicle (P Ͻ 0.01). L-NAME and atropine significantly increased IGP during nutrient infusion compared with vehicle treatment (P Ͻ 0.005 and 0.01, respectively). The effect of PP on IGP during nutrient infusion was abolished in the presence of L-NAME and in the presence of atropine. In vagotomized rats, PP increased IGP compared with intact controls (P Ͻ 0.05). PP significantly delayed gastric emptying of both a noncaloric (P Ͻ 0.05) and a caloric (P Ͻ 0.005) meal. PP inhibits gastric accommodation and delays gastric emptying, probably through inhibition of nitric oxide release. These results indicate that, besides the well-known centrally mediated effects, PP might decrease food intake through peripheral mechanisms. gastric pressure; nutrient tolerance; nitric oxide; vagus nerve BETWEEN MEALS, GASTRIC SMOOTH muscle maintains a high resting tone because of the myoelectrical properties of the smooth muscle but also because of a constant cholinergic input from the vagal nerves. The stomach is known to relax upon food intake. This reflex relaxation, also referred to as gastric accommodation (GA), enables the stomach to receive large quantities of food without an increase in intragastric pressure (IGP) (35). Relaxation of the stomach upon food intake is mediated via vago-vagal reflex pathways, eventually leading to activation of mainly nitrergic nerves in the enteric nervous system (38). Nitric oxide (NO) finally relaxes the smooth muscle cells, and the gastric tone decreases (19).We recently described a method to assess GA in rats by measuring the IGP during intragastric infusion of a liquid test meal (15). During infusion of a test meal, IGP increased initially until an inflection point was reached, after which the IGP stabilized despite further gastric distension. It was suggested that this inflection point represents the onset of...