title: Thioperamide, an H₃ receptor antagonist prevents [³H]glucose uptake in brain of adult rats lesioned as neonates with 5,7-dihydroxytryptamine.
abstract: As a first attempt at exploring an association between histaminergic and serotoninergic neuronal phenotypes in glucose regulation, the influence of the histamine H₃ receptor antagonist thioperamide on glucose uptake by brain was determined in rats in which the serotoninergic innervations of brain was largely destroyed perinatally. Male Wistar rats were initially treated on the 3rd day after birth with the serotoninergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) (75 μg icv) or saline vehicle (10 μl icv). At 8 weeks lesioned and control rats were terminated in order to validate the effectiveness of 5,7-DHT: reduction in 5-HT and 5-HIAA by 83-91% and 69-83% in striatum, frontal cortex, and hippocampus (HPLC/ED method). Other groups of rats were pretreated with thioperamide (5.0 mg/kg ip) or saline vehicle 60 min prior to 6-[³H]-D-glucose (500 μCi/kg ip). Fifteen-min later rats were decapitated and brains were excised and dissected to remove frontal cortex, striatum, hippocampus, thalamus/hypothalamus, pons, and cerebellum. Liquid scintillation spectroscopy was used to determine that [³H]glucose uptake, which was enhanced in 5,7-DHT lesioned rats in cortex (by 88%), hippocampus, thalamus/hypothalamus, pons and cerebellum (each by 47-56%), and in striatum (by 35%). In contrast, thioperamide prevented the enhancement in [³H]glucose uptake in all brain regions of 5,7-DHT neonatally lesioned rats; and [³H]glucose levels were significantly different in all brain regions (except thalamus/hypothalamus) in thioperamide-versus saline-treated rats. These findings indicate a functional association between histaminergic and serotoninergic systems in brain in relation to glucose regulation.
authors.affiliation: Department of Environmental Medicine and Epidemiology, Medical University of Silesia, H.Jordana St. 38, PL 41-808 Zabrze, Poland.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Jośko
authors.forename: Jacek
authors.initials: J
authors.lastname: Drab
authors.forename: Przemysław
authors.initials: P
authors.lastname: Nowak
authors.forename: Ryszard
authors.initials: R
authors.lastname: Szkilnik
authors.forename: Eva
authors.initials: E
authors.lastname: Körossy
authors.forename: Dariusz
authors.initials: D
authors.lastname: Boroń
authors.forename: Halina
authors.initials: H
authors.lastname: Brus
authors.forename: Richard M
authors.initials: RM
authors.lastname: Kostrzewa
authors.forename: Ryszard
authors.initials: R
authors.lastname: Brus
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D054828:Histamine H3 Antagonists / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism / Q000502:physiology; D014316:Tritium / Q000378:metabolism
chemical_list: D054828:Histamine H3 Antagonists; D010880:Piperidines; D014316:Tritium; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; C052075:thioperamide; D005947:Glucose