TY - JOUR
T1 - Adenosine stimulates glycogenolysis in mouse cerebral cortex
T2 - A possible coupling mechanism between neuronal activity and energy metabolism
AU - Magistretti, P. J.
AU - Hof, P. R.
AU - Martin, J. L.
PY - 1986
Y1 - 1986
N2 - 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 μM. Theophylline antagonizes the glycogenolysis induced by adenosine with an EC50 of 80 μM. The rank-order of potencies of adenosine agonists is adenosine 5'-cyclopropyl-carboxamide > 2-chloroadenosine >> 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 μM is inhibited by ouabain at 10 μM, a concentration of the cardiac glycoside not significantly affecting 3H-glycogen levels per se. Interestingly, the previously demonstrated glycogenolytic action of vasoactive intestinal peptide and of norepinephrine 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. 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.
AB - 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 μM. Theophylline antagonizes the glycogenolysis induced by adenosine with an EC50 of 80 μM. The rank-order of potencies of adenosine agonists is adenosine 5'-cyclopropyl-carboxamide > 2-chloroadenosine >> 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 μM is inhibited by ouabain at 10 μM, a concentration of the cardiac glycoside not significantly affecting 3H-glycogen levels per se. Interestingly, the previously demonstrated glycogenolytic action of vasoactive intestinal peptide and of norepinephrine 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. 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.
UR - http://www.scopus.com/inward/record.url?scp=0022918311&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.06-09-02558.1986
DO - 10.1523/jneurosci.06-09-02558.1986
M3 - Article
C2 - 3018195
AN - SCOPUS:0022918311
SN - 0270-6474
VL - 6
SP - 2558
EP - 2562
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 9
ER -