title: Regulation of the anorectic drug recognition site during glucoprivic feeding.
abstract: The acute effects of 2-deoxy-D-glucose (2-DG)-induced glucoprivic feeding on the anorectic drug recognition site and Na+K(+)-ATPase in the brain were examined in adult rats and in lean and genetically obese mice. The marked hyperglycemia and the induction of feeding caused by the administration of 2-DG to satiated rats and lean mice were associated with significant increases in Na+K(+)-ATPase activity, and in [3H]ouabain binding and [3H]mazindol binding to the anorectic drug recognition site in hypothalamic membranes. Basal and 2-DG-stimulated levels of blood glucose were significantly correlated to the levels of hypothalamic [3H]ouabain (r = + .91, p less than 0.01) and [3H]mazindol (r = + .87, p less than 0.01) binding. A significant correlation (r = .74, p less than 0.05) was also observed between [3H]mazindol binding and [3H]ouabain binding supporting the hypothesis that these hypothalamic binding sites are functionally coupled in their response to circulating glucose. Following the intracerebroventricular (ICV) administration of the diabetogenic drug alloxan, 2-DG did not stimulate feeding or increase [3H]mazindol and [3H]ouabain binding sites in the hypothalamic paraventricular area. Since 2-DG still caused hyperglycemia in alloxan-treated rats, alloxan-induced inactivation of glucoreceptor mechanisms led to an uncoupling of the anorectic drug recognition site from a hypothalamic glucostat. In genetically obese mice (ob/ob), 2-DG also could not induce feeding or increase hypothalamic [3H]ouabain or [3H]mazindol binding, despite a significant hyperglycemic response. In contrast, 2-DG did increase feeding and the binding of [3H]ouabain and [3H]mazindol to the hypothalamus of lean littermates.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Clinical Neuroscience Branch, National Institute of Mental Health, NIH, Bethesda, MD 20985.
authors.forename: I
authors.initials: I
authors.lastname: Angel
authors.forename: R L
authors.initials: RL
authors.lastname: Hauger
authors.forename: B A
authors.initials: BA
authors.lastname: Giblin
authors.forename: S M
authors.initials: SM
authors.lastname: Paul
mesh_terms: D000496:Alloxan / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003847:Deoxyglucose / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D008454:Mazindol / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000503:physiopathology*; D009928:Organ Specificity; D010042:Ouabain / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D011956:Receptors, Cell Surface; C027786:glucose receptor; D010042:Ouabain; D000496:Alloxan; D003847:Deoxyglucose; D008454:Mazindol; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose