Possible central adenosinergic modulation of ethanol-induced alterations in [14C]glucose utilization in mice.
The possible role of brain adenosine in acute ethanol-induced alteration in glucose utilization in the whole brain, as well as in the specific brain areas (cerebellum and brain stem), was investigated. Mice were killed 20-min postethanol, and the fresh tissue slices (300 microns) of brain and/or specific brain areas were incubated for 100 min in a 5.5 mM glucose medium in Warburg flasks using [6-(14)C]glucose as a tracer. Trapped 14CO2 was counted to estimate glucose utilization. Ethanol (2 g/kg, i.p.) markedly increased the glucose utilization in whole brain and in both motor areas of brain. Theophylline (50 mg/kg, i.p.), an adenosine antagonist, significantly reduced ethanol-induced increase in glucose utilization in whole brain, as well as in brain areas. However, adenosine agonist N6-cyclohexyladenosine (CHA; 0.1 mg/kg, i.p.) on the contrary, significantly accentuated ethanol-induced increase in glucose utilization in these tissues that was nearly completely blocked by theophylline pretreatment. Theophylline alone did not produce any significant change in glucose utilization, whereas CHA alone (in vivo and in vitro) significantly increased glucose utilization, as well as ethanol-induced increase in glucose utilization in an additive manner. Relevant supportive data were obtained by experiments in which adenosine deaminase (ADA), p-sulfophenyltheophylline (8-SPT), and CHA were administered in vitro to the slice preparations. Both ADA and 8-SPT were effective in almost completely blocking the ethanol-induced increase in glucose utilization, whereas CHA further enhanced the ethanol-induced increase in glucose utilization in an additive manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Anwer
J
J
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Dar
M S
MS
D000241:Adenosine / Q000502:physiology*; D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D001933:Brain Stem / Q000503:physiopathology; D002531:Cerebellum / Q000503:physiopathology; D008297:Male; D051379:Mice; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D001786:Blood Glucose; D018047:Receptors, Purinergic P1; D000241:Adenosine