Journal of Neuroscience, Vol 6, 2558-2562, Copyright © 1986 by Society for Neuroscience
Adenosine stimulates glycogenolysis in mouse cerebral cortex: a possible coupling mechanism between neuronal activity and energy metabolism
PJ Magistretti, PR Hof and JL Martin
Adenosine promotes a concentration-dependent hydrolysis of 3H-glycogen
newly synthesized from 3H-glucose by mouse cerebral cortical slices. The
EC50 for this effect is 7 microM. Theophylline antagonizes the
glycogenolysis induced by adenosine with an EC50 of 80 microM. The rank-
order of potencies of adenosine agonists is adenosine 5'-cyclopropyl-
carboxamide greater than 2-chloroadenosine much greater than N6-
cyclohexyladenosine = adenosine, suggesting that adenosine promotes
glycogenolysis via receptors of the A2 type. This contention is
substantiated by the weak stereospecificity observed for the glycogenolytic
action of D- and L-(phenylisopropyl)-adenosine. The glycogenolysis elicited
by adenosine at 10 and 100 microM is inhibited by ouabain at 10 microM, a
concentration of the cardiac glycoside not significantly affecting
3H-glycogen levels per se. Interestingly, the previously demonstrated
glycogenolytic action of vasoactive intestinal peptide (Magistretti et al.,
1981, 1984) and of norepinephrine (Quach et al., 1978) is also antagonized
by ouabain. These results demonstrate the existence of a metabolic action
of adenosine, which is sensitive to ouabain and appears to be mediated by
A2 receptors. The concentrations at which adenosine promotes glycogenolysis
are of the same order of magnitude as those reached extracellularly by the
nucleoside during neuronal depolarization (Pull and McIlwain, 1972). This
set of observations therefore supports the notion that adenosine plays a
modulatory role in the coupling between neuronal activity and energy
metabolism in the CNS.