title: Chylomicron components activate duodenal vagal afferents via a cholecystokinin A receptor-mediated pathway to inhibit gastric motor function in the rat.
abstract: Nutrients in the intestine initiate changes in secretory and motor function of the gastrointestinal (GI) tract. The nature of the 'sensors' in the intestinal wall is not well characterized. Intestinal lipid stimulates the release of cholecystokinin (CCK) from mucosal entero-endocrine cells, and it is proposed that CCK activates CCK A receptors on vagal afferent nerve terminals. There is evidence that chylomicron components are involved in this lipid transduction pathway. The aim of the present study was to determine (1) the pathway mediating reflex inhibition of gastric motility and (2) activation of duodenal vagal afferents in response to chylomicrons. Mesenteric lymph was obtained from awake rats fitted with lymph fistulas during intestinal perfusion of lipid (Intralipid, 170 micromol h(-1), chylous lymph) or a dextrose and/or electrolyte solution (control lymph). Inhibition of gastric motility was measured manometrically in urethane-anaesthetized recipient rats in response to intra-arterial injection of lymph close to the upper GI tract. Chylous lymph was significantly more potent than control lymph in inhibiting gastric motility. Functional vagal deafferentation by perineural capsaicin or CCK A receptor antagonist (devazepide, 1 mg kg(-1), i.v.) significantly reduced chylous lymph-induced inhibition of gastric motility. The discharge of duodenal vagal afferent fibres was recorded from the dorsal abdominal vagus nerve in an in vitro preparation of the duodenum. Duodenal vagal afferent nerve fibre discharge was significantly increased by close-arterial injection of CCK (1-100 pmol) in 43 of 83 units tested. The discharge of 88% of CCK-responsive fibres was increased by close-arterial injection of chylous lymph; devazepide (100 microg, i.a.) abolished the afferent response to chylous lymph in 83% of these units. These data suggest that in the intestinal mucosa, chylomicrons or their products release endogenous CCK which activates CCK A receptors on vagal afferent nerve fibre terminals, which in turn initiate a vago-vagal reflex inhibition of gastric motor function.
authors.affiliation: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Jörg
authors.initials: J
authors.lastname: Glatzle
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.forename: David W
authors.initials: DW
authors.lastname: Adelson
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Kalogeris
authors.forename: Tilman T
authors.initials: TT
authors.lastname: Zittel
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
authors.forename: Jen-Yu
authors.initials: JY
authors.lastname: Wei
authors.forename: Helen E
authors.initials: HE
authors.lastname: Raybould
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002766:Cholecystokinin / Q000378:metabolism; D002914:Chylomicrons / Q000502:physiology*; D020109:Devazepide / Q000494:pharmacology; D004386:Duodenum / Q000294:innervation*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D008198:Lymph Nodes / Q000502:physiology; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology
chemical_list: D002914:Chylomicrons; D006727:Hormone Antagonists; D043886:Receptor, Cholecystokinin A; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D002766:Cholecystokinin; D020109:Devazepide; D002211:Capsaicin