ADENINE NUCLEOTIDES AND SYNAPTIC TRANSMISSION IN THE in vitro RAT HIPPOCAMPUS
TV Dunwiddie, BJ Hoffer - British journal of pharmacology, 1980 - Wiley Online Library
TV Dunwiddie, BJ Hoffer
British journal of pharmacology, 1980•Wiley Online Library1 The effects of adenosine and various derivatives were examined in the in vitro
hippocampal slice preparation from rat. 2 The amplitudes of extracellularly recorded field
potentials from the CA1 region were depressed by adenosine, and this effect could be
antagonized by methylxanthines. Because presynaptic field potentials were unaffected by
adenosine, while the field epsp was depressed, adenosine would appear to act at a synaptic
site to depress transmission. 3 Adenosine deaminase, which breaks down adenosine to …
hippocampal slice preparation from rat. 2 The amplitudes of extracellularly recorded field
potentials from the CA1 region were depressed by adenosine, and this effect could be
antagonized by methylxanthines. Because presynaptic field potentials were unaffected by
adenosine, while the field epsp was depressed, adenosine would appear to act at a synaptic
site to depress transmission. 3 Adenosine deaminase, which breaks down adenosine to …
- 1The effects of adenosine and various derivatives were examined in the in vitro hippocampal slice preparation from rat.
- 2The amplitudes of extracellularly recorded field potentials from the CA1 region were depressed by adenosine, and this effect could be antagonized by methylxanthines. Because presynaptic field potentials were unaffected by adenosine, while the field e.p.s.p. was depressed, adenosine would appear to act at a synaptic site to depress transmission.
- 3Adenosine deaminase, which breaks down adenosine to inosine, increased the amplitude of synaptic responses, while hexobendine, which blocks reuptake of adenosine, had a depressant effect. This strongly suggests that the endogenous release of adenosine from the hippocampal slice preparation is sufficient to exert a tonic inhibitory influence on the amplitude of synaptic responses.
- 4Cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) and its dibutyryl derivative had depressant effects on the amplitude of field responses which were blocked by theophylline, suggesting that they are able to act at the extracellular adenosine receptor. (−)‐Isoprenaline (which raises tissue cyclic AMP levels), and the 8‐p‐chlorophenylthio derivative of cyclic AMP both increased the amplitude of population spike responses, and these effects were not blocked by theophylline, suggesting that the physiological effects of adenosine are not mediated via a cyclic AMP‐dependent mechanism.
- 5Since adenosine is not the transmitter at this CA1 pyramidal cell synapse, but is apparently present in the extracellular compartment in sufficient concentrations to affect the synaptic physiology of this region, this provides strong evidence in favour of the concept of a neuromodulatory role for adenosine in the central nervous system.
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