title: The source of brain adenosine outflow during ischemia and electrical stimulation.
abstract: Adenosine outflow and adenosine and adenine nucleotide content of hippocampal slices were evaluated under two different experimental conditions: ischemia-like conditions and electrical stimulation (10 Hz). Five minutes of ischemia-like conditions brought about an 8-fold increase in adenosine outflow in the following 5 min during reperfusion, and a 2-fold increase in adenosine content, a 43% decrease in ATP, a 72% increase in AMP and a 30% decrease in energy charge (E.C.) at the end of the ischemic period. After 10 min of reperfusion ATP, AMP and E.C. returned to control values, while the adenosine content was further increased. Five minutes of electrical stimulation brought about an 8-fold increase in adenosine outflow that peaked 5 min after the end of stimulation, a 4-fold increase in adenosine content and an 18% decrease in tissue E.C. at the end of stimulation. After 10 min of rest conditions the adenosine content and E.C. returned to basal values. The origin of extracellular adenosine from S-adenosylhomocysteine (SAH) was examined under the two different experimental conditions. The SAH hydrolase inhibitor, adenosine-2,3-dialdehyde (10 microM), does not significantly modify the adenosine outflow evoked by electrical stimulation or ischemia-like conditions. This finding excludes a significant contribution by the transmethylation pathway to adenosine extracellular accumulation evoked by an electrical or ischemic stimulus, and confirms that the most likely source of adenosine is from AMP dephosphorylation.
authors: Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
authors: S
authors: S
authors: Latini
authors: C
authors: C
authors: Corsi
authors: F
authors: F
authors: Pedata
authors: G
authors: G
authors: Pepeu
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D043383:Adenosylhomocysteinase; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006867:Hydrolases / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012435:S-Adenosylhomocysteine / Q000378:metabolism
chemical_list: D000227:Adenine Nucleotides; C027579:periodate-oxidized adenosine; D012435:S-Adenosylhomocysteine; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000241:Adenosine