Adenosine receptor up-regulation: initiated upon preconditioning but not upheld.

Activation of adenosine receptors is part of the endogenous defense against cerebral hypoxia and ischemia. However, it is not known which adenosine receptor subtypes mediate hypoxic tolerance upon chemical preconditioning. Selective A3 receptor mRNA up-regulation to 135 +/- 34% (mean +/- s.d.; p<0.05) was observed 1 h after preconditioning with 3-nitropropionate while A1 receptor mRNA levels remained unchanged (94 +/- 23%; n.s.). After 24h A3 and A1 receptor mRNA expression were both at control level. Further treatment in vitro resulted in a selective A3 receptor mRNA reduction. We conclude that the early (onset within hours) but not the late (duration of days) neuroprotection upon chemical preconditioning is associated with a selective up-regulation of A3 receptor mRNA. Detection of A3 receptor mRNA is very sensitive to prolonged stress in vitro.