Area Postrema Lesion Alters the Effects of Peptide YY on 2-DG-Stimulated Pancreatic Exocrine Secretion

Previously we demonstrated that circulating peptide YY (PYY), which inhibits pancreatic exocrine secretion, binds to specific receptors in the area postrema (AP); therefore we have tested the hypothesis that the removal of the AP (APX) will alter the effects of PYY on pancreatic secretion in awake rats. One-month after AP lesion or sham lesion, rats were implanted with pancreatic, biliary, duodenal, and intravenous catheters. After recovery from the surgery, unanesthetized rats were infused with vehicle or PYY (30 pmol/kg/hr or 100 pmol/kg/hr) under basal or 2-deoxy-d-glucose (2-DG) stimulated (75 mg/kg, intravenous bolus) conditions. PYY at 30 pmol/kg/hr inhibited basal pancreatic fluid secretion in sham-operated rats, but not APX rats. PYY at 100 pmol/kg/hr stimulated basal pancreatic protein secretion in sham-operated rats, and this effect was also lost in APX rats. PYY at 30 and 100pmol/kg/hr inhibited peak 2-DG stimulated protein secretion to a greater extent in APX rats as compared to sham-operated rats (P < 0.05). Since PYY inhibition of basal pancreatic secretion is AP dependent and inhibition of 2-DG stimulated pancreatic secretion is AP independent, we conclude that the 2-DG pathway of pancreatic secretion differs from the pathway responsible for basal secretion, and that APX potentiates the inhibitory effect of PYY on the 2-DG pathway.