title: Effects of tumor necrosis factor α on leptin-sensitive intestinal vagal mechanoreceptors in the cat.
abstract: The involvement of tumour necrosis factor α (TNF-α) in inflammatory bowel disease (IBD) has been established, and anti-TNF-α has been suggested as a therapeutic approach for the treatment of these pathologies. We studied the effects of TNF-α on leptin-sensitive intestinal vagal units to determine whether TNF-α exerts its effects through the intestinal vagal mechanoreceptors and to investigate its interactions with substances regulating food intake. The activity of intestinal vagal mechanoreceptors was recorded via microelectrodes implanted into the nodose ganglion in anesthetized cats. TNF-α (1 μg, i.a.) increased the discharge frequency of leptin-activated units (type 1 units; P < 0.05) and had no effect on the discharge frequency of leptin-inhibited units (type 2 units). When TNF-α was administered 20 min after sulfated cholecystokinin-8 (CCK), its excitatory effects on type 1 units were significantly enhanced (P < 0.0001) and type 2 units were significantly (P < 0.05) activated. Pre-treatment with Il-1ra (250 μg, i.a.) blocked the excitatory effects of TNF-α on type 1 units whereas the excitatory effects of TNF-α administration after CCK treatment on type 2 units were not modified. The activation of leptin-sensitive units by TNF-α may explain, at least in part, the weight loss observed in IBD.
authors.affiliation: a Aix Marseille Université, Physiologie et Physiopathologie du Système Nerveux Somatomoteur et Neurovégétatif (PPSN, EA4674), Avenue Escadrille Normandie Niemen, 13397 Marseille Cedex 20, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Quinson
authors.forename: Véronique
authors.initials: V
authors.lastname: Vitton
authors.forename: Michel
authors.initials: M
authors.lastname: Bouvier
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Grimaud
authors.forename: Anne
authors.initials: A
authors.lastname: Abysique
mesh_terms: D000758:Anesthesia; D000818:Animals; D002415:Cats; D002766:Cholecystokinin / Q000494:pharmacology; D004558:Electric Stimulation; D055724:Electrophysiological Phenomena / Q000187:drug effects; D053583:Interleukin-1beta / Q000494:pharmacology; D007422:Intestines / Q000187:drug effects* / Q000294:innervation; D020738:Leptin / Q000494:pharmacology*; D008465:Mechanoreceptors / Q000187:drug effects*; D010812:Physical Stimulation; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014630:Vagus Nerve / Q000187:drug effects*
chemical_list: D053583:Interleukin-1beta; D020738:Leptin; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D002766:Cholecystokinin