ESSENTIAL ROLE OF ADENOSINE, ADENOSINE-A1-RECEPTORS, AND ATP-SENSITIVE K+ CHANNELS IN CEREBRAL ISCHEMIC PRECONDITIONING

Preconditioning with sublethal ischemia protects against neuronal dama ge after subsequent lethal ischemic insults in hippocampal neurons, A pharmacological approach using agonists and antagonists at the adenosi ne A1 receptor as well as openers and blockers of ATP-sensitive K+ cha nnels has been combined with an analysis of neuronal death and gene ex pression of subunits of glutamate and gamma-aminobutyric acid receptor s, HSP70, c-fos, c-jun, and growth factors, It indicates that the mech anism of ischemic tolerance involves a cascade of events including lib eration of adenosine, stimulation of adenosine A1 receptors, and, via these receptors, opening of sulfonylurea-sensitive ATP-sensitive K+ ch annels.