title: The long chain fatty acid oleate activates mouse intestinal afferent nerves in vitro.
abstract: Vagal afferents innervating the gastrointestinal tract serve an important nutrient-sensing function, and these signals contribute to satiety. Detection of nutrients occurs largely through the release of mediators from specialized enteroendocrine cells within the mucosa of the gastrointestinal tract. The signaling pathways leading to vagal afferent activation are not clear; however, previous in-vivo studies have implicated a role for cholecystokinin (CCK). We used an in vitro intestinal afferent extracellular recording preparation to study the effect of luminal perfusion of the long chain fatty acid oleate on mouse intestinal afferent activity. Oleate activated intestinal afferents in a concentration-dependent fashion, with an EC50 value of approximately 25 mmol/L. The L-type calcium channel blocker nicardipine attenuated the effect of oleate. Vagotomy resulted in a significant (>60%) reduction of the responses to both oleate and CCK. The CCK-1 receptor antagonist lorglumide nearly abolished responses to CCK and oleate. Our experiments therefore suggest that oleate activates intestinal afferents, with vagal afferents primarily involved; however, nonvagal fibres also contribute. The activation is dependent on CCK release, likely via activation of L-type channels on mucosal enteroendocrine cells, finally resulting in activation of CCK-1 receptors on the afferent terminals.
authors: Department of Medicine and Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 2V7, Canada.
authors: W Andrew
authors: WA
authors: Webster
authors: Michael J
authors: MJ
authors: Beyak
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D019742:Chemokines, CC; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism / Q000601:surgery; D007583:Jejunum / Q000187:drug effects* / Q000294:innervation* / Q000378:metabolism; D008297:Male; D051379:Mice; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009529:Nicardipine / Q000494:pharmacology; D019301:Oleic Acid / Q000494:pharmacology*; D010477:Perfusion; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D014628:Vagotomy / Q000379:methods; D014630:Vagus Nerve / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; C511142:Ccl28 protein, mouse; D019742:Chemokines, CC; D011949:Receptors, Cholecystokinin; D019301:Oleic Acid; D009529:Nicardipine; D011377:Proglumide; C048181:lorglumide