Site and event specific increase of striatal adenosine release by adenosine kinase inhibition in rats.
The effects of the systemically administered adenosine kinase (AK) inhibitor, 5'-deoxy-5-iodotubercidin (5'd-5IT) on the striatal adenosine (ADO) release evoked by the excitotoxin, kainic acid (KA) were examined using rat bilateral striatal microdialysis. Local KA perfusion of one rat striatum caused a significant ipsilateral elevation of striatal ADO levels compared to basal and contralateral (artificial CSF-perfused) striatal ADO levels. KA-evoked striatal ADO release was augmented in animals receiving systemic 5'd-5IT treatment (cumulative dose of 7.5 micromol/kg, i.p.) compared with i.p. vehicle controls. In contrast, 5'd-5IT administration had no significant effect on basal or contralateral (artificial CSF-perfused) striatal ADO levels. Thus, consistent with the hypothesis of 'site and event specific' potentiation of ADO by AK inhibitors, 5'd-5IT unilaterally enhanced ADO levels in the striatum where KA-induced excitotoxic injury evoked endogenous ADO release, but not at the contralateral uninjured striatum.
Britton
D R
DR
Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Mikusa
J
J
Lee
C H
CH
Jarvis
M F
MF
Williams
M
M
Kowaluk
E A
EA
D000241:Adenosine / Q000378:metabolism*; D000248:Adenosine Kinase / Q000037:antagonists & inhibitors*; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014372:Tubercidin / Q000031:analogs & derivatives* / Q000494:pharmacology
C040541:5'-deoxy-5-iodotubercidin; D004791:Enzyme Inhibitors; D000248:Adenosine Kinase; D000241:Adenosine; D014372:Tubercidin; D007608:Kainic Acid