Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning.
Preconditioning with sublethal ischemia protects against neuronal damage after subsequent lethal ischemic insults in hippocampal neurons. A pharmacological approach using agonists and antagonists at the adenosine A1 receptor as well as openers and blockers of ATP-sensitive K+ channels has been combined with an analysis of neuronal death and gene expression of subunits of glutamate and gamma-aminobutyric acid receptors, HSP70, c-fos, c-jun, and growth factors. It indicates that the mechanism of ischemic tolerance involves a cascade of events including liberation of adenosine, stimulation of adenosine A1 receptors, and, via these receptors, opening of sulfonylurea-sensitive ATP-sensitive K+ channels.
Heurteaux
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C
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
Lauritzen
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I
Widmann
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C
Lazdunski
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M
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D007276:Injections, Intraventricular; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D046911:Macromolecular Substances; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000096:biosynthesis; D017470:Receptors, Glutamate / Q000096:biosynthesis; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D018840:HSP70 Heat-Shock Proteins; D046911:Macromolecular Substances; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D018047:Receptors, Purinergic P1; D000255:Adenosine Triphosphate; D000241:Adenosine