Neuropeptide Y in the paraventricular nucleus of the hypothalamus stimulates colonic transit by peripheral cholinergic and central CRF pathways

There is evidence suggesting that neuropeptide Y (NPY) as well as corticotropin-releasing factor (CRF) in the paraventricular nucleus of the hypothalamus (PVN) are involved in the CNS regulation of gastrointestinal (GI) function. We studied the effects of NPY or Y1-and Y2-receptor agonists microinjected into the PVN on colonic transit. Microinjection of NPY into the PVN at doses of 0.15-1.5 microg decreased the colonic transit time of conscious rats up to 49%. Pretreatment with the peripherally acting cholinergic antagonist atropine methyl nitrate (0.1 mg kg-1 i.p.) blocked the NPY into PVN-induced effect on colonic motor function.The agonist of the Y1-receptor, NPY(Leu31, Pro34), as well as the Y2-receptor agonist, NPY(13-36), dose-dependently decreased colonic transit time when microinjected into the PVN (0.05, 0.15 and 0.5 microg). However, the Y1-receptor agonist was more effective. Intracerebroventricular (ICV) application of the CRF-receptor antagonist, alpha-helical-CRF9-41 (50 microg/rat), blocked the NPY effect in the PVN on colonic motor function. In conclusion, stimulation of colonic transit by NPY acting in the PVN was observed. The PVN is more sensitive to agonists acting on the Y1- than on the Y2-receptor to mediate stimulation of propulsive colonic motility. The effect of NPY in the PVN on colonic motor function depends on central CRF and peripheral cholinergic pathways.