The peripheral modulation of duodenal and colonic motility in rats by the pancreatic polypeptide-fold family: neuropeptide Y, peptide YY, and pancreatic polypeptide.

Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) altered intraluminal pressure in the duodenum and colon of fasted anesthetized rats following intravenous bolus administration. There were rapid increases in intraluminal pressure of the duodenum and colon of anesthetized rats following peripheral injections of NPY, PYY and PP. Administration (IV) of NPY, PYY, and PP increased intraduodenal pressure +1.8, +3.2, and +3.7 mmHg compared to saline baseline. Prazosin, an alpha-2 adrenergic antagonist, did not alter the response of the duodenum of urethane-anesthesized rats to any of the PP-fold peptides following peripheral administration. Yohimbine, an alpha 2-adrenergic antagonist, attenuated the excitatory response of rat duodenum following NPY (IV) but did not alter the duodenal response to PP (IV). Intravenous NPY, PYY, and PP increased intracolonic pressure +2.0, +3.3, and +6.2 mmHg compared to saline baseline. In the presence of prazosin, an alpha 1-adrenergic antagonist, the intraluminal pressure of the colon increased +2.6, +2.4, and +8.1 mmHg compared to saline baseline by NPY, PYY, and PP (IV), respectively. In the presence of alpha 2-adrenergic blockade by yohimbine, NPY, PYY, and PP (IV) increased intraluminal pressure of the colon +4.2, +2.9, and +2.5 mmHg compared to saline baseline. The response of the duodenum to the excitatory effect of PYY (IV) was enhanced in the presence of yohimbine. Duodenal and colonic tone were modulated by the PP-fold peptides following peripheral administration. The alpha-adrenergic nervous system played only a minor role in the modulation of GI motility by the PP-fold peptides at peripheral sites.