The modulation of ecto-nucleotidase activities by glutamate in cultured cerebellar granule cells

Several enzymes hydrolyze ATP, producing ADP which is hydrolyzed to AMP. Ec to-5'-nucleotidase produces adenosine from AMP. Glutamate (Glu) is an excit atory neurotransmitter and increases extracellular adenosine levels, which is considered an important inhibitory neuromodulator. Here we show that Glu activates ADP and AMP hydrolysis. NMDA and kainic acid (KA) also increased these enzymatic activities, but 1-aminocyclopentane-1S,3R-dicarboxylic aci d (ACPD) had no effect. Dihydrokainate (DHK), an inhibitor of glutamate upt ake, also blocked glutamate-evoked activation of ecto-nucleotidases, sugges ting that this activation was also Glu transporters dependent. Therefore, w e suggest that the Glu-evoked stimulation of ecto-nucleotidases might contr ibute to the increase of adenosine in extracellular space induced by Glu. N euroReport 11:709-712 (C) 2000 Lippincott Williams & Wilkins.