Premium
Investigations into the Adenosine Outflow from Hippocampal Slices Evoked by Ischemia‐Like Conditions
Author(s) -
Pedata Felicita,
Latini Serena,
Pugliese Anna Maria,
Pepeu Giancarlo
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03566.x
Subject(s) - inosine , adenosine , ischemia , adenosine receptor , chemistry , glutamate receptor , adenosine a1 receptor , medicine , tetrodotoxin , nmda receptor , endocrinology , pharmacology , anesthesia , biology , receptor , biochemistry , agonist
The characteristics of adenosine and inosine outflow evoked by 5 min of ischemia‐like conditions in vitro (superfusion with glucose‐free Krebs solution gassed with 95% N 2 /5% CO 2 ) were investigated on rat hippocampal slices. The viability of the slices after “ischemia” was evaluated by extracellular recording of the evoked synaptic responses in the CA1 region. The evoked dendritic field potentials were abolished after 5 min of superfusion under “ischemia” but a complete recovery occurred after 5 min of reperfusion with normal oxygenated Krebs solution. No recovery took place after 10 min of “ischemia.” The addition of the adenosine A, receptor antagonist 8‐phenylthe‐ ophylline to the superfusate antagonized the depression of the evoked field potentials caused by 5 min of “ischemia.” Five minutes of “ischemia” brought about a six‐ and fivefold increase in adenosine and inosine outflow, respectively, within 10 min. Tetrodotoxin reduced the outflow of adenosine and inosine by 42 and 33%, respectively, whereas the removal of Ca 2+ caused a further increase. The NMDA receptor antagonist d (‐)‐2‐amino‐7‐ phoshonoheptanoic acid and the non‐NMDA antagonist 6,7‐dinitroquinoxaline‐2,3‐dione brought about small, not statistically significant decreases of adenosine and inosine outflow. The glutamate uptake inhibitor dihydrokainate did not affect the outflow of adenosine and inosine. Inhibition of ecto‐5′‐nucleotidase by α, β‐methylene ADP and GMP did not affect basal adenosine outflow but potentiated “ischemia”‐evoked adenosine outflow. It is concluded that ischemia‐like conditions in vitro evoke a Ca 2+ ‐independent adenosine and inosine outflow, through a mechanism that partly depends on propagated nervous activity but does not involve excitatory amino acids. The efflux of adenosine is probably responsible for the depression of the evoked synaptic electrical activity during “ischemia” in the hippocampal slices.