Inhibition of adenosine deaminase activity reveals an intense active transport of adenosine into neurons in primary cultures

Abstract

It is often assumed that adenosine transport into brain cells occurs by facilitated diffusion and that the continued net uptake of adenosine depends on its subsequent metabolism, which keeps the intracellular concentration of unmetabolized adenosine low and thus maintains a concentration gradient. If that is the case, inhibition of adenosine metabolism should decrease uptake. We have previously reported a considerable deamination of accumulated adenosine to inosine in primary cultures of cerebral cortical neurons. A relatively specific adenosine deaminase inhibitor, 2'-deoxycoformycin, was used in the present study. In the presence of this drug, the adenosine content (pool size) increased many fold without any decrease in total influx of adenosine. Influx of accumulated adenosine took place against a concentration gradient, demonstrating that a metabolic degradation of accumulated adenosine is not required to drive adenosine uptake. This does not preclude that under normal conditions some adenosine may get into the cells by diffusion.