Peptide YY (PYY) stimulates intrinsic enteric motor neurones in the rat small intestine

The effects of peptide YY (PYY) on motor activity of the rat small intestine, were studied using isolated organ bath preparations arranged for recording muscle activity in the longitudinal axis. PYY induced TTX sensitive concentration-dependent contractions and/or relaxations of the longitudinal muscle in different regions of the small intestine. In the duodenum PYY evoked only "cholinergic" contractions (3 x 10(-8)-3 x 10(-7) M). In the jejunum, PYY-evoked concentrations were non-cholinergic, and contractions were never seen in the ileum. In the jejunum and ileum, PYY-evoked relaxations (3 x 10(-8)-3 x 10(-7) M) were unaffected by adrenoceptor or cholinergic receptor blockade, thus indicating that these relaxations were mediated by non-adrenergic, non-cholinergic (NANC) inhibitory nerves. Another action of PYY was to cause inhibition of field stimulation-evoked cholinergic concentrations. This inhibitory action was primarily due to antagonism of post-junctional, cholinergic receptor mediated events. In addition, PYY inhibited histamine evoked contractions of the longitudinal muscle. All regions of the small intestine could be desensitized to PYY. Such PYY-densensitization did not affect the ability of the longitudinal muscle to relax in response to applied ATP or papaverine. These results suggest PYY has potent concentration-dependent stimulatory actions at intrinsic inhibitory and excitatory motor nerves. In addition, PYY interferes with contractions but not relaxations of the longitudinal muscle.