title: Intraportal infusion of 2,5-anhydro-D-mannitol increases afferent activity in the common hepatic vagus branch.
abstract: Peripheral administration of the fructose analogue 2,5-anhydro-D-mannitol (AM), that inhibits hepatic glucose release and ATP formation, stimulates food intake in rats. This effect is partly generated in the hepato-portal area and transmitted to the central nervous system by the common hepatic vagus branch because hepatic branch vagotomy eliminated the feeding response to AM. In the present study, we investigated if the pertinent signal to increase food intake changes the discharge rate in hepatic vagal afferents. An in vivo preparation was used to record afferent hepatic vagal activity following intraportal infusion of AM in anaesthetized rats. Fine nerve filaments were isolated from the distal cut end of the hepatic vagus branch. Nerve activity was recorded by a bipolar electrode and analyzed after conversion of raw data to standard pulses. Standard pulses were integrated into spike counts of 5 s duration and the mean number of spikes in a 50 s interval at baseline was compared to spike count 10, 30 and 50 min after infusion of AM (100 or 300 mg/kg) or saline (control). Saline infusion did not influence afferent hepatic vagal activity. Intraportal infusion of AM, however, dose-dependently increased afferent activity in the hepatic vagus branch. In conclusion, AM increased the afferent discharge rate in the common hepatic vagus branch at doses that have previously been shown to increase food intake. These findings agree with the proposed role of fuel metabolism in the hepato-portal area in the control of food intake and with the suggestion that fuel availability controls food intake by influencing the hepatic afferent discharge rate.
authors.affiliation: Institute of Veterinary Physiology, University of Zürich, Switzerland. tomlutz@vetphys.unizh.ch
authors.forename: T A
authors.initials: TA
authors.lastname: Lutz
authors.forename: A
authors.initials: A
authors.lastname: Niijima
authors.forename: E
authors.initials: E
authors.lastname: Scharrer
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004594:Electrophysiology; D007275:Injections, Intravenous; D008099:Liver / Q000294:innervation; D008297:Male; D008353:Mannitol / Q000031:analogs & derivatives* / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D014630:Vagus Nerve / Q000166:cytology* / Q000187:drug effects / Q000502:physiology
chemical_list: D008353:Mannitol; C031765:2,5-anhydromannitol