Aspects of purine receptor function in hippocampal slices

Nikbakht, Mohammad-Reza (2001) Aspects of purine receptor function in hippocampal slices. PhD thesis, University of Glasgow.

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This study is concerned with the effect of adenosine and ATP in the CA1 area of hippocampus and their interaction with muscarinic and N-methyl-D-aspartate (NMDA) receptors. Single and paired-pulse stimuli have been applied to the Schaffer collateral and comissural fibers and recordings were made by a glass microelectrode containing 0.9% NaC1 from stratum pyramidale. The paired-pulse paradigm includes paired-pulse inhibition (PPI) and paired-pulse facilitation (PPF) which provide a more accurate indication of presynaptic events than the study of single population spikes and postsynaptic potentials. This technique has been employed to distinguish presynaptic events from postsynaptic. In paired-pulse experiments, the stimulus intensity of the conditioning pulse (first pulse) and testing pulse (second pulse) stimuli were always the same. The nature of the paired-pulse interaction in the absence of exogenous agents was dependent on the interstimulus intervals between two pairs of stimuli. A biphasic pattern has been observed with inhibition at shorter interstimulus intervals (10ms) and facilitation at longer intervals (20 & 50ms). However in a few slices no facilitation was observed at 20ms. The effect of ATP and its stable analogus on single and paired-pulse responses has been examined. ATP and betagamma-methyleneATP reproduced the effect of adenosine, reducing the paired-pulse inhibition at shorter interstimulus intervals and increasing facilitation at longer stimulus intervals. Their effects were mostly prevented by application of 8-phenyltheophylline (8PT), an A1 receptor antagonist, and adenosine deaminase indicating their mediation by adenosine. The effect of betagamma-methyleneATP was also significantly reduced by suramin 50muM suggesting the possible activation of P2 receptors. It has unexpectedly been found that the qualitative nature of the response to ATP and non-hydrolysable analogue betagamma-methyleneATP was dependent upon the population spike size. When both nucleotides were applied to hippocampal slices having ppoulation sikes with amplitude > 5mV, population spikes were depresed but a significant fade in response has been observed during 10 minutes of perfusion. Suramin prevented the fade, while betagamma-methylene ADP, an inhibitor of 5'-nucleotidase, enhanced the fade supporting the involvement of P2 receptors through the release of endogenous adenosine. It has been concluded that in slices with large population spikes, a part of the inhibitory effect of nucleotides is produced by adenosine generated from the breakdown of nucleotides but another part may result from eindogenous adenosine which is released following activation of P2 receptors. The second part of this thesis was to examine the interaction between adenosine and muscarinic receptors. The last part of this study was to investigate the interaction between adenosine and NMDA receptors activated directly by applied NMDA or indirectly using glycine, applying electrical long term potentiation (LTP) or removing Mg++ from media. The results showed that NMDA receptor activation significantly suppressed the single and paired-pulse responses to adenosine. Overall, the results from this chapter have clearly shown the existence of both adenosine and NMDA receptors on presynaptic nerve terminals where NMDA receptor activation can modulate the effect of adenosine. It seems that an increase in the excitatory action of A2A receptors is more relevant than a depression of A1 receptor function. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Neurosciences.
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Stone, Prof. Trevor
Date of Award: 2001
Depositing User: Enlighten Team
Unique ID: glathesis:2001-73240
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jun 2019 08:56
Last Modified: 28 Oct 2021 15:53
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