The effects of the adenosine reuptake inhibitor soluflazine on synaptic potentials and population hypoxic depolarizations in area CA1 of rat hippocampus in vitro.
Adenosine has recently been shown to play a potentially important role in the regulation of synaptic excitability during experimental hypoxia in the hippocampus of the rat. Endogenous adenosine, rapidly released at the initiation of a hypoxic episode, produced synaptic depression, which could protect sensitive neurons. In the present experiments, an inhibitor of the reuptake of adenosine, soluflazine (R64719) was employed to increase the levels of endogenous adenosine under normoxic and hypoxic conditions in slices of the hippocampus of the rat. Soluflazine produced a slow-onset, concentration-dependent depression of population excitatory postsynaptic potentials, which was reversed by the specific A1 adenosine receptor antagonist, 8-cyclopentyltheophylline. During severe N2-induced hypoxia, soluflazine significantly delayed hypoxic depolarization. These results suggest that inhibition of the reuptake of adenosine may have therapeutic potential in the amelioration of hypoxic/ischemic neuronal damage, particularly in the hippocampus.
Department of Neuropharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492.
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Gribkoff
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D010879:Piperazines; C054695:soluflazine; C053907:8-cyclopentyl-1,3-dimethylxanthine; D013806:Theophylline; D000241:Adenosine