ATP extracellular concentrations are increased in the rat striatum during in vivo ischemia.

Abstract

Interest is growing in the role of adenosine triphosphate (ATP) on P2 receptors during hypoxic/ischemic events in the brain. However, there is no direct evidence of an increase in extracellular ATP levels during cerebral ischemia in vivo. The aim of the present study was to evaluate ATP outflow from the rat striatum by the microdialysis technique associated with focal cerebral ischemia in vivo by intraluminal occlusion of the right middle cerebral artery (MCA). Between 1 and 4h after ischemia, rats showed a clear turning behavior contralateral to the ischemic side. Twenty-four hour after MCA occlusion, ischemic rats had definite neurological deficit and striatal and cortical damage. The ATP concentration (mean+/-S.E.M.) in the striatum of normoxic rats (n = 8) was 3.10+/-0.34 nM. During 220 min after MCA occlusion, the extracellular ATP levels significantly increased two-fold, being 5.90+/-0.61 nM (p < 0.01 versus normoxic level). ATP outflow showed a tendency to increase over time during the 220 min of ischemia. Since extracellular ATP is rapidly metabolized to adenosine, we also assessed ATP outflow in the presence of the ecto-5'-nucleotidase inhibitor, alpha,beta-methylene-adenosine diphosphate (AOPCP, 1 mM) directly perfused into the striatum. The ATP concentration in normoxic rats (n = 8) was increased three-fold in the presence of the ecto-5'-nucleotidase inhibitor (9.57+/-0.26 nM). During 220 min of ischemia, extracellular ATP levels significantly increased 1.3-fold in AOPCP-treated rats (12.62+/-0.65 nM, p < 0.01 versus normoxic level). The present study confirms that ATP is continuously released in the brain and demonstrates for the first time that ATP outflow increases during ischemia in vivo. These results confirm that ATP may be an important mediator in brain ischemia.

• Authors: Alessia Melani, Daria Turchi, Maria Giuliana Vannucchi, Sara Cipriani, Marco Gianfriddo, Felicita Pedata
• Journal: Neurochemistry international (Neurochem Int) Vol. 47 Issue 6 Pg. 442-8 (Nov 2005) ISSN: 0197-0186 [Print] England
• PMID: 16029911 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Receptors, Purinergic P2
• Adenosine Triphosphate
• 5'-Nucleotidase
• Adenosine

Topics

• 5'-Nucleotidase (antagonists & inhibitors, metabolism)
• Adenosine (metabolism)
• Adenosine Triphosphate (metabolism)
• Animals
• Brain Infarction (etiology, metabolism, physiopathology)
• Brain Ischemia (metabolism, physiopathology)
• Corpus Striatum (metabolism, physiopathology)
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Extracellular Fluid (metabolism)
• Infarction, Middle Cerebral Artery (metabolism, physiopathology)
• Male
• Microdialysis
• Movement Disorders (etiology, metabolism, physiopathology)
• Rats
• Rats, Wistar
• Receptors, Purinergic P2 (metabolism)
• Up-Regulation (drug effects, physiology)