INTRAPORTAL INFUSION OF 2,5-ANHYDRO-D-MANNITOL INCREASES AFFERENT ACTIVITY IN THE COMMON HEPATIC VAGUS BRANCH

Peripheral administration of the fructose analogue 2,5-anhydro-D-manni tol (AM), that inhibits hepatic glucose release and ATP formation, sti mulates food intake in rats. This effect is partly generated in the he pato-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 thr pertinent signal to increase food intake changes the discharge rat e in hepatic vagal afferents. An in vivo preparation was used to recor d afferent hepatic vagal activity following intraportal infusion of AM in anaesthetized rats. Fine nerve filaments were isolated from the di stal cut end of the hepatic vagus branch. Nerve activity was recorded by a bipolar electrode and analyzed after conversion of raw data to st andard pulses. Standard purses were integrated into spike counts of 5 s duration and the mean number of spikes in a 50 s interval at baselin e 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 influen ce afferent hepatic vagal activity. Intraportal infusion of AM, howeve r, dose-dependently increased afferent activity in the hepatic vagus b ranch. In conclusion, AM increased the afferent discharge rate in the common hepatic vagus branch at doses that have previously been shown t o increase food intake. These findings agree with the proposed role of fuel metabolism in the hepato-portal area in the control of food inta ke and with the suggestion that fuel availability controls food intake by influencing the hepatic afferent discharge rate.