Saturable binding of circulating peptide YY in the dorsal vagal complex of rats

The rationale for this study was to test the hypothesis that peripherally released peptide YY (PYY) acts in the vagal nuclear complex of the medulla oblongata to modulate vagal tone centrally. The objective was to determine whether circulating PYY gains access to and binds to the receptors identified in the dorsal vagal complex (DVC) under physiological conditions. Specific brain regions were microdissected after intravenous 125I-labeled PYY and 131I-labeled bovine serum albumin infusions to determine saturable accumulation of PYY in the brain and to determine if there were changes in plasma volume with large PYY infusions. Significant (P < 0.05) saturable binding was observed in the region of the brain stem containing the DVC and the pituitary. There were no significant changes in plasma volume in any region after the infusion of the excess nonradioactive PYY. We conclude that under physiological conditions circulating PYY binds to sites in the pituitary and portions of the DVC that have PYY receptors and an incomplete blood-brain barrier but does not bind to other areas that have an intact blood-brain barrier. Therefore this peripheral hormone may act centrally to modulate the digestive system and is a member of a novel class of gut hormones that function as central neuromodulators.