Glucostatic regulation of (+)-[3H]amphetamine binding in the hypothalamus: correlation with Na+,K+-ATPase activity.
Preincubation of rat hypothalamic slices in glucose-free Krebs-Ringer buffer (37 degrees C) resulted in a time-dependent decrease in specific (+)-[3H]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 (+)-[3H]amphetamine binding, whereas incubation with L-glucose, 2-deoxy-D-glucose, or 3-O-methyl-D-glucose failed to increase the number of (+)-[3H]amphetamine binding sites. Ouabain potently inhibited the glucose-induced stimulation of (+)-[3H]amphetamine binding, suggesting the involvement of Na+,K+-ATPase. Preincubation of hypothalamic slices with glucose also resulted in an increase in Na+,K+-ATPase activity and the number of specific "high-affinity" binding sites for [3H]ouabain, and a good correlation was observed (r = 0.89; P less than 0.02) between the glucose-stimulated increase in (+)-[3H]amphetamine and [3H]ouabain binding. Similar increases in (+)-[3H]amphetamine binding, [3H]ouabain binding, and Na+,K+-ATPase activity were observed in the hypothalamus after parenteral administration of glucose to rats. The administration of anorectic doses of amphetamine (0.1-5.0 mg/kg of body weight) also increased Na+,K+-ATPase activity in the hypothalamus. These data suggest that the (+)-[3H]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+,K+-ATPase activity, and the latter may be involved in the "glucostatic" regulation of appetite.
Angel
I
I
Hauger
R L
RL
Luu
M D
MD
Giblin
B
B
Skolnick
P
P
Paul
S M
SM
D000818:Animals; D002352:Carrier Proteins; D003913:Dextroamphetamine / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D002352:Carrier Proteins; D011941:Receptors, Adrenergic; D017981:Receptors, Neurotransmitter; C036062:amphetamine receptor; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D003913:Dextroamphetamine