In vivo effects of adenosine A1 receptor agonist and antagonist on neuronal and astrocytic intermediary metabolism studied with ex vivo 13C NMR spectroscopy.
Adenosine is a neuromodulator, and it has been suggested that cerebral acetate metabolism induces adenosine formation. In the present study the effects that acetate has on cerebral intermediary metabolism, compared with those of glucose, were studied using the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) and antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Fasted rats received an intravenous injection of CCPA, DPCPX, or vehicle. Fifteen minutes later either [1,2-13C]acetate or [1-13C]glucose was given intraperitoneally; after another 30 min the rats were decapitated. Cortical extracts were analyzed with 13C NMR spectroscopy and HPLC analysis. DPCPX affected neuronal and astrocytic metabolism. De novo synthesis of GABA from neuronal and astrocytic precursors was significantly reduced. De novo syntheses of glutamate and aspartate were at control levels, but their degradation was significantly elevated. In glutamine the anaplerotic activity and the amount of label in the position representing the second turn in the tricarboxylic acid cycle were significantly increased, suggesting elevated metabolic activity in astrocytes. CCPA did not influence GABA, aspartate, or glutamine synthesis. In glutamate the contribution from the astrocytic anaplerotic pathway was significantly decreased. In the present study the findings in the [1,2-13C]acetate and [1-13C]glucose control, CCPA, and DPCPX groups were complementary, and no adenosine A1 agonist effects arising from cerebral acetate metabolism were detected.
Håberg
A
A
Department of Anesthesia and Medical Imaging, Trondheim University Hospital, Norway.
Qu
H
H
Haraldseth
O
O
Unsgård
G
G
Sonnewald
U
U
D000085:Acetates / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D002247:Carbon Isotopes; D002540:Cerebral Cortex / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D014020:Tissue Extracts / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology
D000085:Acetates; D000596:Amino Acids; D002247:Carbon Isotopes; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D014020:Tissue Extracts; D014970:Xanthines; C058394:2-chloro-N(6)cyclopentyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D005947:Glucose; D000241:Adenosine