Hyperpolarization of the rat hepatocyte membrane by 2,5-anhydro-D-mannitol in vivo.
The fructose analogue 2,5-anhydro-D-mannitol (2,5-AM), that inhibits glucose release and ATP formation in liver cells, seems to stimulate feeding by acting on the liver, because hepatic portal injection was more effective than jugular vein injection and because hepatic branch vagotomy attenuated 2,5-AM's hyperphagic effect. Russek's "potentiostatic" hypothesis postulates a role for the hepatic membrane potential in the control of food intake with depolarization of hepatocytes signaling hunger and hyperpolarization representing a satiety signal. Therefore, the aim of the present study was to find out, whether 2,5-AM affects the hepatic membrane potential under in vivo conditions. The membrane potential was measured with microelectrodes in anesthetized rats after intraperitoneal (i.p.) or intraportal (i.p.v.) administration of 2,5-AM or control solution. 2,5-AM significantly hyperpolarized the hepatocyte membrane 50 min after i.p. injection (100 mg/kg: 3.6 mV; 300 mg/kg: 9.9 mV). In a second experiment, 2,5-AM (300 mg/kg) elicited a significant hyperpolarization of hepatocytes as soon as 5-9 min after i.p.v. infusion. These effects occurred at doses that have been shown to increase the afferent discharge rate in the common hepatic vagus branch, and to stimulate food intake. 2,5-AM's hyperphagic effect therefore is associated with an increase in the hepatic membrane potential. These findings contradict the predictions of the "potentiostatic" hypothesis and are consistent with the notion, that the feeding response to 2,5-AM might be due to ATP depletion in the terminals of vagal afferents.
Lutz
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Institute of Veterinary Physiology, University of Zurich, Switzerland. tomlutz@vetphys.unizh.ch
Boutellier
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Scharrer
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D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D008353:Mannitol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley
D008353:Mannitol; C031765:2,5-anhydromannitol