Peptide YY inhibits cholecystokinin-stimulated sphincter of Oddi activity in the prairie dog.

Peptide YY (PYY), a recently discovered gut peptide, has been shown to have a number of actions that are antagonistic to the effects of cholecystokinin. This study was designed to determine whether PYY would inhibit cholecystokinin-stimulated sphincter of Oddi activity in the prairie dog. In 12 prairie dogs PYY was infused intravenously at 1, 10, and 100 ng/kg/min, and arterial blood samples were obtained. A dose-response curve was obtained, with the 10 ng/kg/min dose producing serum levels of 725 pg/ml. In seven additional prairie dogs a side-hole, pressure-monitored perfusion catheter was passed into the duodenum through a choledochotomy and positioned in the sphincter of Oddi. A perfusion catheter was also placed in the gallbladder fundus. Sphincter of Oddi and gallbladder pressures were recorded before and during 20-minute infusions of cholecystokinin and then cholecystokinin plus PYY at 10 ng/kg/min. PYY significantly inhibited cholecystokinin-stimulated sphincter of Oddi phasic wave frequency (3.8 +/- 0.2 vs 3.3 +/- 0.4; p less than 0.05) and sphincter of Oddi motility index (26.2 +/- 4.3 vs 18.7 +/- 4.8; p less than 0.025) but did not affect the increase in gallbladder pressure induced by cholecystokinin. These findings are consistent with other known anticholecystokinin effects of PYY. We conclude that PYY may also inhibit sphincter of Oddi activity in the prairie dog by an anticholecystokinin effect, thus reducing flow through the sphincter.