Saturation of neuroprotective effects of adenosine in cortical culture.
Adenosine and adenosine A1 receptor agonists are often, but not always, protective against metabolic insults. The effects of an A1 agonist and antagonist on neuronal death were determined in cortical cell cultures. The A1 agonist cyclohexyladenosine did not attenuate neuronal death induced by oxygen-glucose deprivation, but did attenuate death caused by glucose deprivation or NMDA. Extracellular adenosine levels during oxygen-glucose deprivation were significantly higher than those during glucose deprivation or NMDA exposure. The A1 antagonist 8-cyclopentyltheophylline increased death induced by oxygen-glucose deprivation, but not that caused by glucose deprivation or NMDA exposure. Thus, while activation of A1 receptors can provide neuroprotection, the protective effect appears to become saturated by high levels of endogenous extracellular adenosine during oxygen-glucose deprivation.
Lobner
Doug
D
Department of Biomedical Sciences and Integrative Neuroscience Research Center, Marquette University, 561 N. 15th Street, Rm 426, Milwaukee, WI 53233, USA. doug.lobner@marquette.edu
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D018929:Cell Culture Techniques; D016923:Cell Death; D002540:Cerebral Cortex / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005110:Extracellular Space / Q000378:metabolism; D005947:Glucose / Q000172:deficiency; D000860:Hypoxia; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; C053907:8-cyclopentyl-1,3-dimethylxanthine; C048599:N(6)-cyclopentyladenosine; D016202:N-Methylaspartate; D013806:Theophylline; D005947:Glucose; D000241:Adenosine