Glucostatic regulation of (+)-(/sup 3/H)amphetamine binding in the hypothalamus: correlation with Na/sup +/, K/sup +/-ATPase activity
Preincubation of rat hypothalamic slices in glucose-free Krebs-Ringer buffer (37/sup 0/C) resulted in a time-dependent decrease in specific (+)-(/sup 3/H)amphetamine binding in the crude synaptosomal fraction prepared from these slices. The addition of D-glucose resulted in a dose- and time-dependent stimulation of (+)-(/sup 3/H)amphetamine binding, whereas incubations with L-glucose, 2-deoxy-D-glucose, or 3-O-methyl-D-glucose failed to increase the number of (+)-(/sup 3/H)amphetamine binding sites. Ouabain potently inhibited the glucose-induced stimulation of (+)-(/sup 3/H)amphetamine binding, suggesting the involvement of Na/sup +/, K/sup +/-ATPase. Preincubation of hypothalamic slices with glucose also resulted in an increase in Na/sup +/,K/sup +/-ATPase activity and the number of specific high-affinity binding sites for (/sup 3/H)ouabain, and a good correlation was observed between the glucose-stimulated increase in (+)-(/sup 3/H)amphetamine and (/sup 3/H)ouabain binding. These data suggest that the (+)-(/sup 3/H)amphetamine binding site in hypothalamus, previously linked to the anorectic actions of various phenylethylamines, is regulated both in vitro and in vivo by physiological concentrations of glucose. Glucose and amphetamine appear to interact at common sites in the hypothalamus to stimulate Na/sup +/,K/sup +/-ATPase activity, and the latter may be involved in the glucostatic regulation of appetite.
- Research Organization:
- National Institutes of Health (NIH), Bethesda, MD (United States)
- OSTI ID:
- 6300715
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 82:18
- Country of Publication:
- United States
- Language:
- English
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ENZYME ACTIVITY
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OUABAIN
RATS
ACID ANHYDRASES
ALDEHYDES
ANALEPTICS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
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CARDIAC GLYCOSIDES
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CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
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HEXOSES
HYDROLASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MONOSACCHARIDES
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PHOSPHOHYDROLASES
RODENTS
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STROPHANTHINS
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