The effect of cyclohexyladenosine on the periischemic increases of hippocampal glutamate and glycine in the rabbit.
We investigated the ability of N6-cyclohexyladenosine (CHA), a potent and selective agonist of the adenosine A1 receptor, to attenuate elevations of levels of extracellular hippocampal glutamate and glycine that result from episodes of transient global cerebral ischemia (TGCI). A total of 30 New Zealand white rabbits were randomly assigned to receive 0 (n = 5), 0.1 (n = 8), 1.0 (n = 6), 10 (n = 6), or 100 (n = 5) microM CHA. The drug was dissolved in artificial CSF (vehicle) and administered via a microdialysis probe placed stereotactically into the dorsal hippocampus. A second microdialysis probe placed into the contralateral hippocampus of each animal was perfused with vehicle alone. Ten minutes of TGCI was induced by neck tourniquet inflation and deliberate hypotension from 0 to 10 min. Microdialysis samples were collected as follows: every 20 min preischemia (at -80, -60, -40, -20, and 0 min); every 5 min during ischemia and in the immediate reperfusion period (at 5, 10, 15, and 20 min); and every 20 min for the remainder of the reperfusion period (at 40, 60, and 80 min). Samples were then analyzed for their concentration of glutamate and glycine by HPLC. Following 10 min of ischemia, glutamate levels increased to a peak of 3.28 +/- 0.55 times baseline and returned to preischemic levels by 40 min, i.e., during reperfusion. Glycine concentrations increased to 5.41 +/- 0.91 times over baseline and remained elevated for the duration of the study.(ABSTRACT TRUNCATED AT 250 WORDS)
Neuroanesthesia Research Laboratory, University of California, San Diego 92093-0818.
S L
SL
Cantor
M H
MH
Zornow
L P
LP
Miller
T L
TL
Yaksh
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D005971:Glutamates / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid; D005998:Glycine / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D011817:Rabbits
D005971:Glutamates; C027513:N(6)-cyclohexyladenosine; D018698:Glutamic Acid; D000241:Adenosine; D005998:Glycine