THE SOURCE OF BRAIN ADENOSINE OUTFLOW DURING ISCHEMIA AND ELECTRICAL-STIMULATION

Adenosine outflow and adenosine and adenine nucleotide content of hipp ocampal slices were evaluated under two different experimental conditi ons: 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% inc rease 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. ret urned to control values, while the adenosine content was further incre ased. Five minutes of electrical stimulation brought about an 4-fold i ncrease in adenosine outflow that peaked 5 min after the end of stimul ation, a 4-fold increase in adenosine content and an 18% decrease in t issue 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 examine d under the two different experimental conditions. The SAH hydrolase i nhibitor, adenosine-2,3-dialdehyde (10 mu M), does not significantly m odify the adenosine outflow evoked by electrical stimulation or ischem ia-like conditions. This finding excludes a significant contribution b y the transmethylation pathway to adenosine extracellular accumulation evoked by an electrical or ischemic stimulus, and confirms that the m ost likely source of adenosine is from AMP dephosphorylation.