Abstract |
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 microM(-1) mM), and was exacerbated by a high concentration of the selective A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine ( CPT; 10 microM). 5-IT (1 microM) 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 A1 receptor.
|
Authors | J J Lynch 3rd, K M Alexander, M F Jarvis, E A Kowaluk |
Journal | Neuroscience letters
(Neurosci Lett)
Vol. 252
Issue 3
Pg. 207-10
(Aug 21 1998)
ISSN: 0304-3940 [Print] Ireland |
PMID | 9739997
(Publication Type: Journal Article)
|
Chemical References |
- Enzyme Inhibitors
- Purinergic P1 Receptor Antagonists
- 8-cyclopentyl-1,3-dimethylxanthine
- Theophylline
- Adenosine Kinase
- Glucose
- Adenosine
|
Topics |
- Adenosine
(pharmacology)
- Adenosine Kinase
(antagonists & inhibitors)
- Animals
- Cell Hypoxia
(physiology)
- Cells, Cultured
- Drug Evaluation, Preclinical
- Enzyme Inhibitors
(pharmacology)
- Glucose
(deficiency)
- Neocortex
(cytology, drug effects)
- Neuroglia
(drug effects)
- Neurons
(drug effects)
- Purinergic P1 Receptor Antagonists
- Rats
- Rats, Sprague-Dawley
- Theophylline
(analogs & derivatives, pharmacology)
|