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PMID: 7753861 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 10 ·1995-05-09 ·Pages 4666-70

Heurteaux C, Lauritzen I, Widmann C, Lazdunski M

Abstract

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.

MeSH Terms
Adenosine/analogs & derivatives,pharmacology,physiology Adenosine Triphosphate/pharmacology Animals Brain-Derived Neurotrophic Factor Cerebral Ventricles/drug effects,physiology Gene Expression HSP70 Heat-Shock Proteins/biosynthesis Hippocampus/drug effects,pathology,physiopathology Injections, Intraventricular Ischemic Attack, Transient/pathology,physiopathology Macromolecular Substances Male Nerve Growth Factors/biosynthesis Nerve Tissue Proteins/biosynthesis Neurons/drug effects,pathology,physiology Potassium Channels/drug effects,physiology Proto-Oncogene Proteins c-fos/biosynthesis Proto-Oncogene Proteins c-jun/biosynthesis Purinergic P1 Receptor Agonists Purinergic P1 Receptor Antagonists Pyramidal Cells/drug effects,pathology,physiology Rats Rats, Wistar Receptors, GABA/biosynthesis Receptors, Glutamate/biosynthesis Receptors, Purinergic P1/physiology Time Factors
Chemicals
Brain-Derived Neurotrophic Factor HSP70 Heat-Shock Proteins Macromolecular Substances Nerve Growth Factors Nerve Tissue Proteins Potassium Channels Proto-Oncogene Proteins c-fos Proto-Oncogene Proteins c-jun Purinergic P1 Receptor Agonists Purinergic P1 Receptor Antagonists Receptors, GABA Receptors, Glutamate Receptors, Purinergic P1 Adenosine Triphosphate Adenosine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Heurteaux C
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
Lauritzen I
Widmann C
Lazdunski M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.10.4666
Published
1995-05-09
Pages
4666-70
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC42005
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.92.10.4666 PMC Full Text View journal details
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