title: 2,5-Anhydro-D-mannitol increases hepatocyte calcium: implications for a hepatic hunger stimulus.
abstract: The fructose analogue, 2,5-anhydro-D-mannitol (2,5-AM), triggers feeding in rats via a mechanism linked to its ability to trap phosphate and deplete hepatic ATP. This metabolic inhibitor is particularly useful in the study of the role of the liver in initiation of feeding as its effects are preferentially localized to the liver, and its metabolic consequences have been extensively characterized. To determine whether changes in intracellular calcium may participate in a mechanism conveying information about hepatic energy status to the nervous system, we studied the effects of 2,5-AM on intracellular calcium in isolated hepatocytes using the ratiometric indicator, fura-2. 2,5-AM elicited a marked elevation of intracellular calcium within 2-3 min of exposure that returned to baseline upon removal of the agent. Removal of external calcium failed to prevent this response, while emptying intracellular stores prevented it. These data are consistent with the hypothesis that hepatic energy status may be conveyed to the nervous system via a calcium-mediated secretion event.
authors.affiliation: Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104-3308, USA. rawson@monell.org
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Rawson
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.forename: Mark I
authors.initials: MI
authors.lastname: Friedman
mesh_terms: D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000172:deficiency / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005456:Fluorescent Dyes; D016257:Fura-2; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006815:Hunger / Q000187:drug effects / Q000502:physiology*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D005456:Fluorescent Dyes; D008353:Mannitol; C031765:2,5-anhydromannitol; D002118:Calcium; D016257:Fura-2