Running head: Pancreatic polypeptide and gastric motility in rats

24 Introduction. Pancreatic polypeptide (PP) is an anorexigenic hormone released from 25 pancreatic F-cells upon food intake. We aimed to determine the effect of PP on 26 gastric accommodation and gastric emptying in conscious Wistar HAN rats to 27 investigate whether effects on motor function could contribute to its anorexigenic 28 effects. Methods. Intragastric pressure (IGP) was measured through a chronically 29 implanted gastric fistula during the infusion of a nutrient meal (Nutridrink; 0.5 ml 30 min). Rats were treated with PP (0, 33 and 100 pmol kg min) in combination with 31 L-N-arginine methyl ester (L-NAME; 180 mg kg h), atropine (3 mg kg h) or 32 vehicle. Furthermore, the effect of PP was tested after subdiaphragmal vagotomy of 33 the stomach. Gastric emptying of a non-caloric and a caloric meal after treatment 34 with 100 pmol kg min PP or vehicle was compared using X-rays. Results. PP 35 significantly increased IGP during nutrient infusion compared to vehicle (p<0.01). L36 NAME and atropine significantly increased IGP during nutrient infusion as compared 37 to vehicle treatment (p<0.005 and <0.01 respectively). The effect of PP on IGP during 38 nutrient infusion was abolished in the presence of L-NAME and in the presence of 39 atropine. In vagotomized rats, PP increased IGP compared to intact controls 40 (p<0.05). PP significantly delayed gastric emptying of both a non-caloric (p<0.05) and 41 a caloric meal (p<0.005). Conclusion. PP inhibits gastric accommodation and delays 42 gastric emptying, probably through inhibition of nitric oxide release. These results 43 indicate that, besides the well-known centrally-mediated effects, PP might decrease 44 food intake through peripheral mechanisms. 45 46