Site and event specific increase of striatal adenosine release by adenosine kinase inhibition in rats

The effects of the systemically administered adenosine kinase (AK) inhibito r, 5'-deoxy-5-iodotubercidin (5'd-5IT) on the striatal adenosine (ADO) rele ase evoked by the excitotoxin, kainic acid (KA) were examined using rat bil ateral striatal microdialysis. Local KA perfusion of one rat striatum cause d a significant ipsilateral elevation of striatal ADO levels compared to ba sal and contralateral (artificial CSF-perfused) striatal ADO levels. KA-evo ked striatal ADO release was augmented in animals receiving systemic 5'd-5I T treatment (cumulative dose of 7.5 mu mol/kg, i.p.) compared with i.p. veh icle controls. In contrast, 5'd-5IT administration had no significant effec t on basal or contralateral (artificial CSF-perfused) striatal ADO levels. Thus, consistent with the hypothesis of 'site and event specific' potentiat ion of ADO by AK inhibitors, 5/d-5IT unilaterally enhanced ADO levels in th e striatum where KA-induced excitotoxic injury evoked endogenous ADO releas e, but not at the contralateral uninjured striatum. (C) 1999 Elsevier Scien ce Ireland Ltd. All rights reserved.