PEPTIDE YY STIMULATES CIRCULAR MUSCLE CONTRACTIONS OF THE ISOLATED-PERFUSED CANINE ILEUM BY INHIBITING NITRIC-OXIDE RELEASE AND ENHANCING ACETYLCHOLINE-RELEASE

Peptide YY (PYY) and neuropeptide Y (NPY), infused into the quiescent isolated perfused canine ileum, dose-dependently increased phasic acti vity of the circular muscle and decreased tonic output of immunoreacti ve vasoactive intestinal peptide (VIP) in the venous effluent. The con tractions subsided before the prolonged inhibition of VIP output. Moto r excitation by PYY, an abundant neuropeptide in this tissue, was redu ced by blockade of muscarinic or nicotinic receptors, or inhibition of nitric oxide (NO) synthase, despite continued inhibition of VIP outpu t. A combination of atropine and hexamethonium eliminated the PYY-indu ced decrement in VIP output and left motor excitation unchanged. Block ade of NO synthase eliminated motility increases under these condition s. Intracellular microelectrode recordings of myenteric plexus-free ci rcular muscle strips found no effect of NPY on the resting membrane po tential, or on the field stimulation-induced inhibitory junction poten tial. Inhibition of VIP release plays no essential role in changing mo tility. These results suggest that PYY/NPY induce motility by stimulat ing release of acetylcholine and inhibiting NO release at a locus prox imal to but not on nerve terminals.