The response of isolated duodenum to neuropeptide Y (NPY) was studied isotonically in neonatal and adult rats. Neuropeptide Y (10(-8) to 10(-6) M) elicited a biphasic contraction of isolated duodenum from neonatal rats, but monophasic and weak contraction of adult duodenum. The first phase of NPY-induced contraction of neonatal duodenum was concentration dependent and partially inhibited by preincubation with tetrodotoxin, a Na+ channel blocker, hyoscine, a muscarinic antagonist, suramin, a P2 purinoceptor antagonist, and indomethacin, an inhibitor for prostaglandin biosynthesis. Neuropeptide Y(13-36), a specific Y2 NPY receptor agonist, elicited a concentration-dependent contraction of neonatal rat duodenum. The duodenal response to NPY thus changes during development in rats. Both cholinergic and purinergic transmission and prostaglandin biosynthesis may be involved in the NPY-induced contraction of neonatal duodenum. Neuropeptide Y-induced contraction may be mediated through presynaptic Y2 receptors.