Aminoglucose-induced feeding suppression is regulated by hypothalamic neuronal histamine in rats.
Central mechanisms involved in feeding suppression produced by 1-deoxy-D-glucosamine (1-DGlcN) and 1-deoxy-N-acetylglucosamine (1-DGlcNAc) are unclear. To clarify the mechanisms, we investigated the role of hypothalamic neuronal histamine (HA) in feeding suppression induced by 1-DGlcN and 1-DGlcNAc in rats. Food intake was suppressed for 3 days after a single infusion of 24 mumol 1-DGlcN into the third cerebroventricle (i.c.v.). Depletion of presynaptic HA due to intraperitoneal infusion (i.p.) of alpha-fluoromethylhistidine (FMH), a specific inhibitor of the HA synthesizing enzyme histidine decarboxylase (HDC), abolished feeding suppression completely. Blockade of postsynaptic H1-receptors by i.p. injection of 26 mumol chlorpheniramine also abolished the suppression. Oral administration of 2.4 mmol 1-DGlcNAc suppressed food intake. However, depletion of neuronal HA due to FMH did not affect the suppression. I.c.v. infusion of 24 mumol 1-DGlcN increased turnover rate of HA at 1 h after the infusion. Hypothalamic HA concentration, but not that of tele-methylhistamine (t-MH), increased at 24 h after i.c.v. infusion of 1-DGlcN, which suggests a correlation between HA concentration and the behavioral response. These results indicate that 1-DGlcN, but not 1-DGlcNAc, modulates feeding suppression through HA neurons in the hypothalamus. Differences in mechanisms of feeding suppression by these aminoglucoses may depend on the principal sites of action in the brain and/or peripheral organs.
Kang
M
M
Department of Internal Medicine I, School of Medicine, Oita Medical University, Japan.
Yoshimatsu
H
H
Kurokawa
M
M
Oohara
A
A
Sakata
T
T
D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002744:Chlorpheniramine / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006632:Histamine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D001067:Appetite Depressants; D001786:Blood Glucose; D006634:Histamine H1 Antagonists; C047200:1-deoxyglucosamine; D002744:Chlorpheniramine; C054284:alpha-fluoromethylhistamine; C086406:1-deoxy-N-acetylglucosamine; D006632:Histamine; D006640:Histidine Decarboxylase; D005944:Glucosamine; D000117:Acetylglucosamine