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.