EurekaMag.com logo
+ Translate

Regulation of the anorectic drug recognition site during glucoprivic feeding


, : Regulation of the anorectic drug recognition site during glucoprivic feeding. Brain Research Bulletin 28(2): 201-208

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 < 0.01) and [3H]mazindol (r = + .87, p < 0.01) binding. A significant correlation (r = .74, p < 0.05) was also observed [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. The dissociation of the anorectic drug recognition site from blood glucose responses to 2-DG suggests that the glucoprivic feeding response in obese mice is impaired. In conclusion, the [3H]mazindol recognition site and the neuronal Na+KP+-ATPase KP+-ATPase labelled by [3H]ouabain binding constitutes a glucoreceptive system which is response to changes in circulating glucose levels modulates feeding. Since the coupling of this anorectic drug recognition site to brain glucostats is defective in genetically obese mice, this system may have an important role in pathological hyperphagia and the development of obesity.

Accession: 002477282

PMID: 1317740

DOI: 10.1016/0361-9230(92)90180-6

Download PDF Full Text: Regulation of the anorectic drug recognition site during glucoprivic feeding


Submit PDF Full Text

No spam - Every submission is manually reviewed

Due to poor quality, we do not accept files from Researchgate

Submitted PDF Full Texts will always be free for everyone
(We only charge for PDFs that we need to acquire)

Select a PDF file:
Close
Close

Related references

Angel, I.; Stivers, J.A.; Paul, S.M.; Crawley, J.N., 1987: Site of action of anorectic drugs: glucoprivic- versus food deprivation-induced feeding. Feeding induced by 2-deoxyglucose was compared with feeding induced by food deprivation in terms of antagonism by anorectic drugs and of anatomical site of action. Glucoprivic feeding was completely blocked by microinjection of amphetamine, fenflu...

Angel I.; Goldman M.E.; Paul S.M., 1986: Defective glucostatic regulation of anorectic drug recognition sites and sodium potassium atpase in genetically obese mice. Society for Neuroscience Abstracts 12(2): 795

Angel, I.; Kiss, A.; Stivers, J.A.; Skirboll, L.; Crawley, J.N.; Paul, S.M., 1986: Regulation of [3H]mazindol binding to subhypothalamic areas: involvement in glucoprivic feeding. The distribution of low-affinity sodium-sensitive binding sites of [3H]mazindol were studied in rat hypothalamic nuclei. Using microdissection methods, it was demonstrated that the highest level of [3H]mazindol binding is localized to the paravent...

Angel I.; Kiss A.; Stivers J.A.; Skirboll L.; Crawley J.N.; Paul S.M., 1986: Regulation of tritiated mazindol binding to subhypothalamic areas involvement in glucoprivic feeding. The distribution of low-affinity sodium-sensitive binding sites of [3H]mazindol were studied in rat hypothalamic nuclei. Using microdissection methods, it was demonstrated that the highest level of [3H]mazindol binding is localized to the paravent...

Angel, I., 1990: Central receptors and recognition sites mediating the effects of monoamines and anorectic drugs on feeding behavior. Clinical Neuropharmacology 13(5): 361-391

Kanatani, A.; Ishihara, A.; Iwaasa, H.; MacNeil, D.J.; Fukami, T., 2006: Development of anorectic NPY antagonists: possible roles of Y1 and Y5 receptors in feeding regulation. Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica 127(2): 88-91

Kraly, F.S.; Blass, E.M., 1974: Motivated feeding in the absence of glucoprivic control of feeding in rats. Feeding to decreased intracellular glucose utilisation was assessed in rats with bilateral damage to the medial forebrain bundle. Rats with brain damage that did not feed to glucoprivation after injections of 2-deoxy-D-glucose, those that ate norm...

Aravich P.F.; Sladek C.D., 1985: Glucoprivic feeding and vasopressin. Society for Neuroscience Abstracts 11(1): 53

Rowland, N.E.; Bellush, L.L.; Carlton, J., 1985: Metabolic and neurochemical correlates of glucoprivic feeding. Various hypotheses are reviewed concerning the mechanisms of feeding induced by insulin or 2DG. New data are presented to show that elevated plasma ketone levels are not sufficient to suppress 2DG feeding, suggesting that nourishment of the brain...

Aravich, P.; Doerries, L.; Stanley, E.M.tcalf, A.L.uterio, T., 1989: Glucoprivic feeding and activity-based anorexia in the rat. Annals of the New York Academy of Sciences75(575): 490-492