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) increased duodenal and colonic intraluminal pressure of urethane-anesthetized rats following intravenous (iv) bolus injections. Increases in mean arterial pressure (MAP) accompanied the excitatory effects of NPY and PYY on gastrointestinal motility in these rats during the same time period. Atropine attenuated PYY's excitatory effect on duodenal pressure of rats. Excitatory effects of NPY, PYY, and PP (iv) on rat colon were not mediated via the muscarinic receptors. In the presence of hexamethonium, a nicotinic antagonist, PP (iv) increased colonic pressure to a greater extent than when administered alone. This observation suggested that PP had an inhibitory effect on colonic motility, which was not apparent as a result of the larger excitatory component. The nicotinic antagonist did not modulate the effects of peripherally administered NPY or PYY on duodenal or colonic motility in anesthetized rats. The Y2 receptor ligand, NPY (13–36) (iv) (500 pmol/kg), increased duodenal 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 Y2 receptors. NPY and PYY (iv) initially increased MAP, which then return to baseline values. Unlike NPY and PYY (iv) which produced short-term hypertensive effects, PP (iv) decreased MAP. Atropine did not attenuate the hypertensive 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 MAP were not altered in the presence of hexamethonium. MAP in anesthetized rats was not modulated by NPY (13–36) (iv). Peripheral modulation of MAP by the PP-fold peptides does not correspond with alterations in gastrointestinal motility observed in these studies.Key words: pancreatic polypeptide-fold peptides, duodenum, colon, atropine.