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NEUROREGULATION AND MOTILITY

Slowing of intestinal transit by fat or peptide YY depends on -adrenergic pathway

¹Gastrointestinal Motility Program and Section of Nutrition, Divisions of Gastroenterology and ²Cardiology, Department of Medicine Cedars-Sinai Medical Center, Cedars-Sinai Medical Center Burns and Allen Research Institute, Los Angeles 90048; and ³David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90024

Submitted 20 May 2003 ; accepted in final form 18 July 2003

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 -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 (₁-adrenoreceptor antagonist) but not phentolamine (-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 ₁-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 -adrenergic pathway and that this adrenergic pathway acts on serotonergic and opioid pathways.

enteric neurons; ileal brake; serotonin; opioid; myenteric plexus

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