Adenosine metabolism in neurons and astrocytes in primary cultures

Abstract

Metabolic fate of [8-14C]adenosine was studied in primary cultures of either astrocytes or neurons from the mouse brain. In astrocytes the main metabolic route was the formation of nucleotides. Thus, synthesis of adenosine triphosphate (ATP) amounted to about 0.2 nmol X min-1 X mg-1 protein. The deamination occurred less rapidly. The total rate of formation of inosine was difficult to establish because a considerable amount of labeled inosine accumulated in the medium. The initial incorporation of radioactivity into inosine in the medium was extremely rapid, probably because of the action of an ectoenzyme. However, the labeling of inosine in the medium also continued to increase slowly throughout the incubation, maybe as a result of release of intracellularly formed inosine. The total inosine formation rate during the incubation amounted to at most 0.1 nmol X min-1 X mg-1. Hypoxanthine was formed at a corresponding rate but was released to a lesser extent. In neurons much less label was incorporated into ATP. The major metabolite was inosine, formed intracellularly at a rate of 0.2 nmol X min-1 X mg-1. In addition, there was an immediate rapid labeling of inosine (and to a lesser extent hypoxanthine) in the medium, again suggesting the action of an ectoenzyme. Neither neurons nor astrocytes released a measurable amount of nucleotides to the medium. The cellular differences in adenosine metabolism are probably of relevance for the interpretation of adenosine metabolism in brain in situ. The ectoenzyme may be of importance for rapid termination of the neuromodulator activity of adenosine, and the rapid nucleotide formation in astrocytes is in agreement with a high metabolic activity of these cells.

Rat cultured astrocytes release guanine-based purines in basal conditions and after hypoxia/hypoglycemia

“…A similar shift has been described for nervous tissue slices (Lloyd and Fredholm., 1995). These data also underline the efficient metabolism of adenine-based purines by astrocyte membranes, as previously reported (Matz and Hertz, 1989;Lai and Wong, 1991;Ciccarelli et al 1994) and the enormous capability of cultured astrocytes to rapidly metabolize the large amounts of extracellular adenine-based purines released under pathological conditions. This tends to restrain the extracellular concentration of adeninebased purines after metabolic insults.…”

Energy Metabolic Changes in the Early Post-injury Period Following Traumatic Brain Injury in Rats

“…One limitation of the rapid-freezing technique employed in the present report is that no information is available regarding the cell types involved in the energy metabolic changes. Although ATP content may be higher in astrocytes versus neurons [67], other techniques may be used to establish whether the observed changes in energy metabolism differ among neurons and glial cells.…”

Involvement of astrocytes in purine‐mediated reparative processes in the brain

“…2), either guanosine monophosphate (GMP) or adenosine monophosphate (AMP). The activity of this nucleotide cycle, considered as the main salvage pathway of nucleosides, was demonstrated in the brain Lowenstein, 1976, 1978) and dominates in neurons (Matz and Hertz, 1989). The most prominent metabolic pathway for nucleoside metabolism in astrocytes is the direct synthesis of nucleotides by adenosine/guanosine kinase Hertz, 1989, 1990).…”