Human pancreatic polypeptide, neuropeptide Y and peptide YY reduce the contractile motility by depressing the release of acetylcholine from the myenteric plexus of the guinea pig ileum.

Transmural stimulation (TS; 15 V, 0.5 msec, 1-5 Hz, for 30 sec) caused a contraction in a frequency-dependent manner of the longitudinal muscle with myenteric plexus of the guinea pig ileum. Two-min premedication with human pancreatic polypeptide (HPP, 10(-8) M-10(-6) M), neuropeptide Y (NPY, 10(-8) M-10(-6) M), and peptide YY (PYY, 10(-8) M-10(-6) M) partially, by less than 35%, reduced TS (15 V, 0.5 msec, 10 Hz)-evoked contraction in a dose-dependent manner without affecting the resting tensions. Hexamethonium, phentolamine, prazocine, yohimbine, propranolol, naloxone and theophylline had no effects on the inhibitory actions of these peptides on TS-evoked contractions. TS (15 V, 0.5 msec, 10 Hz)-evoked 3H-ACh release was significantly reduced by 2-min premedication of HPP (10(-6) M), NPY (10(-6) M) and PYY (10(-6) M). The order of potency of these depressant effects on TS-evoked contraction and 3H-ACh release was PYY greater than NPY greater than HPP. It is suggested that the members of PP family have inhibitory effects on the contractile motility by depressing ACh release from myenteric plexus of the guinea pig ileum.