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 (EC) at the end of th e ischemic period. After 10 min of reperfusion ATP, AMP and EC returne d to control values, while the adenosine content was further increased . Five minutes of electrical stimulation brought about an 8-fold incre ase in adenosine outflow that peaked 5 min after the end of stimulatio n, a 4-fold increase in adenosine content and an 18% decrease in tissu e EC at the end of stimulation. After 10 min of rest conditions the ad enosine content and EC returned to basal values. The origin of extrace llular adenosine from S-adenosylhomocysteine (SAH) was examined under the two different experimental conditions. The SAH hydrolase inhibitor , adenosine-2,3-dialdehyde (10 mu M), does not significantly modify th e adenosine outflow evoked by electrical stimulation or ischemia-like conditions. This finding excludes a significant contribution by the tr ansmethylation pathway to adenosine extracellular accumulation evoked by an electrical or ischemic stimulus, and confirms that the most like ly source of adenosine is from AMP dephosphorylation.