PYY immunoneutralization does not alter lipid-induced inhibition of gastric emptying in rats

Abstract

PYY is released from the distal ileum by fat and may be involved in mediating lipid-induced inhibition of gastric acid secretion and intestinal motility. The role of PYY in intestinal lipid-induced inhibition of gastric emptying in awake rats was investigated using a specific polyclonal antibody raised against PYY. Methods: Gastric emptying of liquids was measured in awake rats fitted with a Thomas gastric cannula. Intralipid (total dose 50 or 100 mg) was perfused for 10 min (0.05 ml/min) into a duodenal ( n=11) or mid-intestinal cannula (60 cm from Ligament of Treitz; n=8), and gastric emptying was measured over the 5–10 min period. Gastric emptying was measured 15 min after IP injection of PYY (1 nmol/rat). PYY antibody (20 mg) or a control antibody (anti-KLH; keyhole limpet hemocyanin) was injected ip 8–12 h before experiments. Results: Exogenous PYY (1 nmol) inhibited gastric emptying and administration of PYY antibody blocked this response. Perfusion of lipid (50 and 100 mg) into the proximal intestine produced a 46% and 66% inhibition of gastric emptying respectively. Inhibition of gastric emptying in response to 50 mg lipid in the proximal small intestine was unaffected by administration of PYY antibody but was abolished by administration of the CCK A receptor antagonist devazepide (0.1 mg/kg ip). Perfusion of lipid into the distal intestine (50 and 100 mg) inhibited gastric emptying by 10% and 32% respectively. Inhibition of gastric emptying in response to 100 mg lipid in the distal intestine was unaffected by PYY antibody. Conclusions: Lipid perfused into either the proximal or distal intestine inhibits gastric emptying via a PYY-independent mechanism. CCK is involved in proximal lipid induced inhibition of gastric emptying.