Biomedical subjects

M R Nikbakht

Publications and source records attributed to M R Nikbakht.

5 recordsLinked to original sources

PubMed2001

Suppression of presynaptic responses to adenosine by activation of NMDA receptors.

The interactions between adenosine and NMDA receptors has been investigated using the paired-pulse paradigm in hippocampal slices. This technique allows the study of drug effects specifically at presynaptic terminals. The inhibitory effect of adenosine on population spikes, and the decrease of paired-pulse inhibition assessed using either population spikes or population excitatory postsynaptic potentials, were suppressed by performing the experiments in magnesium-free medium, or by superfusion of the slices with N-methyl-D-aspartate (NMDA) at a concentration (4 microM) which did not itself affect potential size. The suppressant effect of NMDA was prevented by 2-amino-5-phosphonopentanoic acid. All these interactions were still seen in the presence of bicuculline methobromide, 30 microM. Neither alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) nor kainate produced a suppression of adenosine responses. The presence of NMDA did not modify the effects of baclofen on population potentials or paired-pulse inhibition. Activating NMDA receptors by the induction of long-term potentiation or by superfusion with glycine also reduced significantly the effects of adenosine on population spikes and paired-pulse interactions. Increasing population potential size by a mechanism which did not involve the activation of NMDA receptors (increasing stimulus strength) did not change sensitivity to adenosine. When adenosine receptor-selective agonists were tested, it was found that NMDA did not modify the inhibitory effect of the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine, but did enhance the excitatory effect of the adenosine A(2A) receptor agonist 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680). The combined response to NMDA and CGS21680 was prevented by the adenosine A(2A) receptor selective antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385). It is concluded that NMDA receptor activation can suppress neuronal sensitivity to adenosine by acting at presynaptic sites, and that this interaction results from an increase in the excitatory action of adenosine A(2A) receptors, rather than a depression of A(1) receptor function.

Action Potentials↗

PubMed2000

Presynaptic P2 receptors?

Although the emphasis in ATP research has been on postjunctional receptors, there is also evidence for presynaptic receptors regulating transmitter release in the autonomic nervous system. Recent work has attempted to identify similar mechanisms in the central nervous system. Some of the existing results can be explained by the metabolism of nucleotides to adenosine or adenosine 5'-monophosphate (AMP). However, studies of presynaptic effects using sensitive electrophysiological tests such as paired-pulse interactions indicate that nucleotides can act at presynaptic sites, but that their effects may be mediated by a release of adenosine. Results are also described which indicate that, under some conditions, nucleotides can mediate phenomena such as long-term potentiation, which probably involves a significant presynaptic element. In part these effects may involve a nucleotide-induced release of adenosine and the simultaneous activation of P1 and P2 receptors.

Adenosine Triphosphate↗

PubMed2000

Complex hippocampal responses to ATP: fade due to nucleotidase inhibition and P2-receptor-mediated adenosine release.

When ATP or the related stable analogue, betagamma-imidoATP, were applied to rat hippocampal slices showing population spikes larger than 5 mV peak-to-peak amplitude, a depression of spike size was obtained, which showed a marked fade during the 10-min period of superfusion. The inhibitory responses were prevented by adenosine deaminase or 8-phenyltheophylline. Adenosine responses showed no fade. alphabeta-MethyleneADP enhanced the fade, while suramin at 50 micrometer prevented the early component of the responses. The results suggest that in slices with large population spikes, inhibitory responses to nucleotides are partly due to their conversion to adenosine, and partly due to the activation of P2 receptors which trigger the release of endogenous adenosine.

5'-Nucleotidase↗

PubMed2000

Suramin-sensitive suppression of paired-pulse inhibition by adenine nucleotides in rat hippocampal slices.

In order to assess the possible presence of presynaptic P2 receptors for nucleotides in the hippocampus, adenosine triphosphate and betagamma-methyleneATP have been examined on paired-pulse inhibition in rat hippocampal slices. Both compounds reproduced the effects of adenosine and reduced the amount of paired-pulse inhibition at an interpulse interval of 10 ms and increased the amount of facilitation at intervals of 20 and 50 ms. These effects were prevented by 8-phenyltheophylline and adenosine deaminase, indicating their mediation by adenosine. The effects were also reduced by suramin at 50 microM, suggesting the possible activation of P2 receptors. It is suggested that a population of P2 receptors may exist which promote the release of endogenous adenosine in the hippocampus.

Action Potentials↗

PubMed1999

Occlusive responses to adenosine A1 receptor and muscarinic M2 receptor activation on hippocampal presynaptic terminals.

There is substantial evidence for an interaction between adenosine A1 and muscarinic M1/M3 receptors in some tissues, either at the level of the receptors themselves or at the associated transduction system. We have now addressed the question of whether there is a similar interaction between A1 and presynaptic M2 receptors in the hippocampus. The effects of cyclopentyladenosine (CPA) were studied alone or in combination with the M2 receptor agonist oxotremorine-M. The ability of both to depress synaptic transmission presynaptically at the concentrations used was confirmed using paired-pulse inhibition. When combined at a range of concentrations, the effects of the two agents were less than additive, suggesting that they are acting by a common transduction system. The results indicate that the modulatory, antagonistic effects of A1 adenosine receptors are exerted not only on postjunctional M1/M3 receptors but also at M2 presynaptic receptors.

Adenosine↗