Purine level regulation during energy depletion associated with graded excitatory stimulation in brain.
OBJECTIVE
The formation and release of adenosine following graded excitatory stimulation of the brain may serve important physiological functions such as sleep regulation, as well as an early resistance mechanism against excitotoxicity. However, adenosine at high levels may reflect merely the results of obstructed energy metabolism.


METHODS
We examined the extent to which levels of adenosine and adenylate energy charge are affected in vivo by graded excitatory stimulations of brain using unilateral intrastriatal injections of glutamatergic agents and head-focused high energy microwaving for accurate and precise measures of purines.


RESULTS
Our results confirmed that adenosine levels rise when adenylate energy charge decreases and showed that these increases occurred in three distinct phases with the rate of adenosine formation in each phase increasing as tissue adenylate energy charge was further depleted. In addition, we observed that, in most cases, the effects of focal excitatory stimulation on changes in tissue purine levels were restricted spatially within the immediate vicinity of the injection site; however, when strongly depolarizing stimuli were used, changes in purine levels could be observed in adjacent and, occasionally, even in contralateral brain regions.


CONCLUSIONS
These results provide new insight into purine regulation that occurs under physiologically relevant conditions, such as sleep and during the early stages of brain insults that induce excitotoxicity.
Shepel
P Nickolas
PN
Department of Pharmacology and Therapeutics, University of Manitoba Faculty of Medicine, Winnipeg, Manitoba, R3E 0W3, Canada.
Ramonet
David
D
Stevens
Patrick
P
Geiger
Jonathan D
JD
D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000528:radiation effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects* / Q000528:radiation effects*; D016371:Cranial Irradiation / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004734:Energy Metabolism / Q000187:drug effects / Q000528:radiation effects; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology*; D007839:Functional Laterality; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D008872:Microwaves; D011687:Purines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012043:Regression, Psychology; D013997:Time Factors
D000227:Adenine Nucleotides; D018683:Excitatory Amino Acid Agents; D011687:Purines; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; C030985:purine