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)

journal_name

Brain Res Bull

journal_title

Brain research bulletin

authors

Angel I,Hauger RL,Giblin BA,Paul SM

doi

10.1016/0361-9230(92)90180-6

keywords:

subject

Has Abstract

pub_date

1992-02-01 00:00:00

pages

201-7

issue

2

eissn

0361-9230

issn

1873-2747

pii

0361-9230(92)90180-6

journal_volume

28

pub_type

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