PERIPHERAL MODULATION OF DUODENAL AND COLONIC MOTILITY AND ARTERIAL-PRESSURE BY NEUROPEPTIDE-Y, NEUROPEPTIDE-Y FRAGMENT-13-36, PEPTIDE YY, AND PANCREATIC-POLYPEPTIDE IN RATS - CHOLINERGIC MECHANISMS

The pancreatic polypeptide-fold (PP-fold) peptides neuropeptide Y (NPY ), peptide YY (PYY), and pancreatic polypeptide (PP) (500 pmol/kg) inc reased duodenal and colonic intraluminal pressure of urethane-anesthet ized rats following intravenous (iv) bolus injections. Increases in me an arterial pressure (MAP) accompanied the excitatory effects of NPY a nd PYY on gastrointestinal motility in these rats during the same time period. Atropine attenuated PYY's excitatory effect on duodenal press ure of rats. Excitatory effects of NPY, PYY, and PP (iv) on rat colon were not mediated via the muscarinic receptors. In the presence of hex amethonium, a nicotinic antagonist, PP (iv) increased colonic pressure to a greater extent than when administered alone. This observation su ggested that PP had an inhibitory effect on colonic motility, which wa s not apparent as a result of the larger excitatory component. The nic otinic antagonist did not modulate the effects of peripherally adminis tered NPY or PYY on duodenal or colonic motility in anesthetized rats. The Y-2 receptor ligand, NPY (13-36) (iv) (500 pmol/kg), increased du odenal and colonic pressure in rats to the same extent as the full NPY molecule. Therefore, the peripheral effect of PYY and NPY on duodenal and colonic motility in rats may be mediated via Y, receptors. NPY an d PYY (iv) initially increased MAP, which then return to baseline valu es. Unlike NPY and PYY (iv) which produced short-term hypertensive eff ects, PP (iv) decreased MAP. Atropine did not attenuate the hypertensi ve effects of PYY and NPY (iv); however, the hypotensive effect of PP (iv) was blocked by atropine. The effects of the PP-fold peptides on M AP were not altered in the presence of hexamethonium. MAP in anestheti zed rats was not modulated by NPY (13 - 36) (iv). Peripheral modulatio n of MAP by the PP-fold peptides does not correspond with alterations in gastrointestinal motility observed in these studies.