. Slowing intestinal transit by PYY depends on serotonergic and opioid pathways. Am J Physiol Gastrointest Liver Physiol 286: G558-G563, 2004; 10.1152/ ajpgi.00278.2003.-Slowing of intestinal transit by fat is abolished by immunoneutralization of peptide YY (PYY), demonstrating a key role for this gut peptide. How PYY slows intestinal transit is not known. We tested the hypothesis that the slowing of intestinal transit by PYY may depend on an ondansetron-sensitive serotonergic pathway and a naloxone-sensitive opioid pathway. In a fistulated dog model, occluding Foley catheters were used to compartmentalize the small intestine into proximal (between fistulas) and distal (beyond midgut fistula) half of gut. Buffer (pH 7.0) was perfused into both proximal and distal gut, and PYY was delivered intravenously. Ondansetron or naloxone was mixed with buffer and delivered into either the proximal or distal half of gut. Intestinal transit was measured across the proximal half of the gut. The slowing of intestinal transit by PYY was abolished when either ondansetron or naloxone was delivered into the proximal, but not the distal gut, to localize the two pathways to the efferent limb of the slowing response. In addition, 5-HT slows intestinal transit with marker recovery decreased from 76.2 Ϯ 3.6% (control) to 33.5 Ϯ 2.4% (5-HT) (P Ͻ 0.0001) but was reversed by naloxone delivered into the proximal gut with marker recovery increased to 79.9 Ϯ 7.2% (P Ͻ 0.0005). We conclude that the slowing of intestinal transit by PYY depends on serotonergic neurotransmission via an opioid pathway. ileal brake; intestinal motility; 5-HT; enteric nervous system PEPTIDE YY (PYY), a distal gut peptide released in response to a fatty meal, slows intestinal transit when administered intravenously (47). In addition to this slowing effect on intestinal transit, PYY is considered an inhibitory peptide, because it suppresses gastrin-stimulated acid secretion (1, 42), pancreatic exocrine secretion (1, 40), CCK release (41), and gastric emptying (47). These inhibitory effects of exogenous PYY suggest that it may be responsible for the ileal brake (49), a response that suppresses the digestive activities of the upper gastrointestinal tract when nutrients such as fat reach the distal gut. Immunoneutralization studies (38) confirmed that PYY is a key mediator of the slowing of intestinal transit by the fat-induced ileal brake. It is not known, however, how PYY slows intestinal transit.Previously, we created a fistulated dog model that divided the small intestine into proximal and distal segments. We used it to show that placing fat in the distal half of small intestine slowed transit in the proximal half of small intestine. Because the luminal content of the proximal and distal intestinal segments were not in continuity, this observation indicated that the fat-induced ileal brake occurred via a reflex, whereby the distal segment exposed to fat served as the afferent limb of the reflex and the proximal segment in which intestinal transit was measured serv...

Although the enteric reflex pathway triggered by volume distension is known to depend on an adrenergic nerve, it is not known whether the slowing of intestinal transit by fat or peptide YY (PYY) also depends on an adrenergic pathway. The aim of this study was to test the hypotheses that the slowing of transit by fat or PYY may depend on a beta-adrenergic pathway, and this adrenergic pathway may act via the serotonergic and opioid pathways previously observed for the slowing of transit by fat. Eighteen dogs were equipped with duodenal and midgut fistulas. The small intestine was compartmentalized into the proximal and distal half of gut. The role of adrenergic, serotonergic, and opioid pathways was then tested in the slowing of intestinal transit by fat, PYY, and norepinephrine. Intestinal transit results were compared as the cumulative percent marker of recovery over 30 min. We found that the slowing of transit by fat, PYY, or norepinephrine was reversed by propranolol. In addition, the slowing effect of fat was reversed by metoprolol (beta1-adrenoreceptor antagonist) but not phentolamine (alpha-adrenoreceptor antagonist). Furthermore, norepinephrine-induced slowing of transit was reversed by ondansetron (5-HT3 receptor antagonist) or naloxone (opioid receptor antagonist). Extending these physiological results, we also found by immunohistochemistry that beta1-adrenoreceptors are expressed by neurons of the intrinsic plexuses of the small intestine. We conclude that the slowing of intestinal transit by fat or PYY depends on a beta-adrenergic pathway and that this adrenergic pathway acts on serotonergic and opioid pathways.

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