title: Endogenous adenosine deaminase does not modulate synaptic transmission in rat hippocampal slices under normoxic or hypoxic conditions.
abstract: Field and intracellular potentials were recorded from CA1 pyramidal stratum in submerged slices (at 33 degrees). During "normal" oxygenation (95% O2 + 5% CO2), tonic depression of population spikes and field excitatory postsynaptic potentials by endogenous adenosine was demonstrated by (i) the marked enhancement by the adenosine antagonists 8-(p-sulfophenyl)theophylline (10 microM) and caffeine (0.2 mM), (ii) depression by the transport blocker dipyridamole (5 microM), and (iii) enhancement by exogenous adenosine deaminase (all tested by bath application). Thus, adenosine deaminase (0.5 units/ml) reduced by 10.7 +/- 3.0% (S.E.) the half-maximal stimulus intensity (for population spikes). The effects of adenosine deaminase were prevented by the specific inhibitor, deoxycoformycin (30 microM). In intracellular recordings, excitatory postsynaptic potentials were enhanced in a comparable manner by adenosine deaminase. By contrast, neither deoxycoformycin (5 and 30 microM) nor erythro-9-(2-hydroxy-3-nonyl)adenine (another adenosine deaminase inhibitor; 10 and 50 microM) had significant effects on population spikes. Superfusion with anoxic medium (saturated with 95% N2 + 5% CO2) for 2-3 min suppressed population spikes reversibly, by a mechanism involving adenosine, because 8-(p-sulfophenyl)theophylline (10 microM) and caffeine (0.2 mM) delayed the onset of anoxic block and accelerated the subsequent recovery, and the recovery was much slower or incomplete in the presence of dipyramidole (0.5 microM). However, the anoxic suppression of population spikes was not affected by deoxycoformycin (30 microM) or erythro-9-(2-hydroxy-3-nonyl)adenine (10 microM); the corresponding 50% postanoxic recovery times were also unchanged (e.g. 4.0 +/- 0.2 min for controls and 4.1 +/- 0.3 min in deoxycoformycin).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Anaesthesia Research Department, McGill University, Montréal, Québec, Canada.
authors.forename: P J
authors.initials: PJ
authors.lastname: Zhu
authors.forename: K
authors.initials: K
authors.lastname: Krnjević
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000494:pharmacology / Q000502:physiology*; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D004594:Electrophysiology; D006624:Hippocampus / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D015649:Pentostatin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D009435:Synaptic Transmission / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D058892:Adenosine Deaminase Inhibitors; D015649:Pentostatin; C010192:9-(2-hydroxy-3-nonyl)adenine; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D000243:Adenosine Deaminase; D000225:Adenine