2,5-Anhydro-D-mannitol increases hepatocyte sodium: transduction of a hepatic hunger stimulus?
To test the hypothesis that decreased hepatocyte ATP is transduced into a hepatic neuronal signal via a change in sodium pump activity, we examined the effect of 2,5-anhydro-D-mannitol (2,5-AM), which stimulates feeding behavior in rats, on intracellular sodium levels using 23Na nuclear magnetic resonance (NMR) spectroscopy. Isolated hepatocytes suspended in agarose beads were superfused with either 2.5 mM 2,5-AM or fructose in the presence of the paramagnetic shift reagent, thulium(III)(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylenephosphonate)). Superfusion with 2,5-AM decreased hepatocyte ATP and increased intracellular sodium levels compared with superfusion with either fructose or shift reagent alone starting within 15 min of exposure, reaching a maximum level of 120% of baseline by 30 min and declining gradually thereafter over the next 90 min. Superfusion with fructose, which also decreased hepatocyte ATP but by less than half the amount seen with 2,5-AM, had no significant effect on cellular sodium levels. The results support the hypothesis that changes in sodium pump activity could participate in transducing a hunger stimulus associated with hepatocyte energy status into a signal for hunger.
Friedman
Mark I
MI
Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA. friedman@monell.org
Graczyk-Millbrandt
Grazyna
G
Ji
Hong
H
Rawson
Nancy E
NE
Osbakken
Mary D
MD
D000255:Adenosine Triphosphate / Q000172:deficiency; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005632:Fructose / Q000378:metabolism / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D006815:Hunger / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008353:Mannitol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D005632:Fructose; D008353:Mannitol; C031765:2,5-anhydromannitol; D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase