Adenosine stimulates glycogenolysis in mouse cerebral cortex: a possible coupling mechanism between neuronal activity and energy metabolism

Abstract

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.

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

“…In fact, the activation of adenosine receptors can modify the primary metabolism of most cell types (see [1]) and this is also true for both neurons and astrocytes [101,102] and in particular for the control of glygogen metabolism [51, 103,104]. However, it still remains to be explored if this modulation of brain metabolism by adenosine receptors is implicated in the neuromodulatory or neuroprotective properties of adenosine or if it might be related with the trophic effects of purines (see [105]).…”

Adenosine A2B receptor activation stimulates glucose uptake in the mouse forebrain

“…There are two additional cloned adenosine receptors, the A 2B and the A 3 receptors [12], but their roles have been less explored in the brain. Notably, A 2B R have been implicated in peripheral glucose homeostasis [15,16] and have been proposed to control astrocytic glycogen metabolism [17,18]. Furthermore, we recently observed that A 2B Rs control A 1 receptor (A 1 R)-mediated responses in hippocampal glutamatergic synapses [19].…”

Biochemical quantification of total brain glycogen concentration in rats under different glycemic states

“…Concentrations of brain glycogen can be further influenced by neurotransmitters (Magistretti et al, 1986;Pellerin and Magistretti, 1994) and anesthetics (Nelson et al, 1968;Nordstrom and Siesjo, 1978). Apparently, the degree of brain glycogen increase seems to be related to the depth, duration, and type of anesthesia used, with pentobarbital producing greater increases in glycogen content than, for example, ether (Nelson et al, 1968).…”