Inhibition of adenosine kinase during oxygen-glucose deprivation in rat cortical neuronal cultures

• Published in: Neuroscience letters Vol. 252; no. 3; pp. 207 - 210
• Main Authors: Lynch III, James J, Alexander, Karen M, Jarvis, Michael F, Kowaluk, Elizabeth A
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 21.08.1998; Elsevier
• Subjects: 5-Iodotubercidin; Adenosine; Adenosine - pharmacology; Adenosine kinase; Adenosine Kinase - antagonists & inhibitors; Animals; Biological and medical sciences; Cell Hypoxia - physiology; Cells, Cultured; Drug Evaluation, Preclinical; Enzyme Inhibitors - pharmacology; Glucose - deficiency; Hypoglycemia; Hypoxia; Ischemia; Medical sciences; Neocortex - cytology; Neocortex - drug effects; Neuroglia - drug effects; Neurology; Neurons - drug effects; Purinergic P1 Receptor Antagonists; Rats; Rats, Sprague-Dawley; Theophylline - analogs & derivatives; Theophylline - pharmacology; Vascular diseases and vascular malformations of the nervous system; Hypoxia; Adenosine; 5-Iodotubercidin; Ischemia; Hypoglycemia; Adenosine kinase; Cerebral cortex; Rat; Central nervous system; Cardiovascular disease; Environmental factor; Vascular disease; Cerebrovascular disease; Oxygen; Nervous system diseases; Enzyme; Transferases; Rodentia; Enzyme inhibitor; In vitro; Cerebral disorder; Vertebrata; Experimental disease; Mammalia; Animal; Central nervous system disease; Brain (vertebrata)
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(98)00376-0

Adenosine kinase (AK) inhibitors potentiate the actions of endogenous adenosine (ADO) and ameliorate cerebral ischemic damage in animal models. The present study examined the effects of the AK inhibitor, 5-iodotubercidin (5-IT) in an in vitro model of neuronal ischemia, specifically, combined oxygen-glucose deprivation of rat cortical mixed neuronal-glial cultures. Oxygen-glucose deprivation caused extensive neuronal loss which was accompanied by a marked increase in ADO release into the extracellular medium, was ameliorated by exogenous ADO (10 μM–1 mM), and was exacerbated by a high concentration of the selective A 1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 10 μM). 5-IT (1 μM) had no effect on extracellular ADO levels nor on neuronal loss. However, AK activity in these cultures was markedly suppressed during oxygen-glucose deprivation. Taken together, these data demonstrate a marked down-regulation of AK activity during oxygen-glucose deprivation in this in vitro model, providing an endogenous mechanism contributing to the accumulation of extracellular ADO, which exerts neuroprotective effects by activating the ADO A 1 receptor.