Adenosine inhibits epileptiform activity arising in hippocampal area CA3

Ault, Brian; Wang, Ching M.

doi:10.1111/j.1476-5381.1986.tb14587.x

Cited by 95 publications

(38 citation statements)

References 56 publications

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“…The present results confirm the existence of a powerful purinergic inhibitory tonus in area CA3 of the hippocampus [1] which appears to be exclusively mediated via Arreceptors. The selective blockade of Al-receptors induced epileptiform discharges in area CA3 resembling those observed following suppression of GABAergic inhibition [11] or elevation of the extracellular potassium concentration [3].…”

supporting

confidence: 83%

Transient and selective blockade of adenosine A1-receptors by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) causes sustained epileptiform activity in hippocampal CA3 neurons of guinea pigs

Alzheimer

Sutor

Bruggencate

1989

Neuroscience Letters

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The effects of endogenously released adenosine on the excitability of hippocampal neurons were studied using the novel and highly selective adenosine A~-receptor antagonist 8-cyclopentyl-l,3-dipropylxanthine (DPCPX), Extra-and intracellular recordings performed in area CAI and CA3 of the guinea pig hippocampal slice preparation revealed that a transient suppression of an inhibitory purinergic tonus by DPCPX leads to sustained interictal-like epileptiform activity arising in area CA3. Once induced, the spontaneous burst discharges were apparently irreversible within the observation period, even after prolonged washout (2-3 h) in normal solution. In contrast, the hyperpolarizing action of exogenous adenosine, which was substantially reduced by DPCPX, recovered within 3(Y60 min of drug washout, indicating that DPCPX was not irreversibly bound to the Arreceptor.Several lines of evidence suggest the existence of an inhibitory purinergic tonus on CNS neurons generated by the release of endogenous adenosine [4][5][6][7]. The action of adenosine is mediated by specific receptors which have been classified into A1-and A2-subtypes [6]. However, electrophysiological investigations of the effects of adenosine on CNS neurons have been hampered by the lack of selective antagonists able to distinguish selectively between adenosine Ai-and A2-receptors [4,6]. Therefore, the recent development of the highly selective, competitive Al-receptor antagonist 8-cyclopentyl-l,3-dipropylxanthine (DPCPX), which has a 700-fold A1 selectivity [9], should provide a useful tool to separate the various actions of adenosine in terms of receptor subtype activation.Slices (500/zm) were prepared from the guinea pig hippocampus and kept submerged in bathing solution (30-31°C) containing (in mM): NaC1 121, KC1 3,

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supporting

confidence: 83%

Transient and selective blockade of adenosine A1-receptors by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) causes sustained epileptiform activity in hippocampal CA3 neurons of guinea pigs

Alzheimer

Sutor

Bruggencate

1989

Neuroscience Letters

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“…Kainic acid-induced (rat prepiriform cortex) seizures Anticonvulsant effect [214] Kindling (rat amygdala, caudate nucleus) model Seizure reduction [119,272] Pentylenetetrazole-induced (intraperitoneal injection) seizures in rats Seizure reduction [256] Bicuculline-induced (rat prepiriform cortex) seizures Seizure protection [267] Bicuculline-induced (rat hippocampal slices) epileptiform activity Decreased epileptiform activity [168] Bicuculline …”

Section: Ado Receptor Agonistsmentioning

confidence: 99%

“…Kindling (rat amygdala, and hippocampus) model Seizure suppression, seizure prevention [115,116,213,[258][259][260] Pilocarpine-induced (intraperitoneal injection) seizures in rats Blocked seizure appearance [258,261] Pilocarpine-induced (hippocampus) seizures in rats Seizure protection [262] Lithium-pilocarpine-induced status epilepticus in rats Protective effect [216] Pentylenetetrazole-induced (intravenous application) seizures in rats Increased seizure threshold [265] Pentylenetetrazole-induced (intraperitoneal injection) seizures in rats Partial seizure protection [204] Pentylenetetrazole-induced (intraperitoneal injection) seizures in mice Increased seizure latency [118] Pentylenetetrazole-induced seizures in rats Suppressed/abolished tonic phase of generalized tonicclonic seizures [255] Kainic acid-induced (intraperitoneal injection) seizures in mice Increased seizure latency [118] Electroshock-induced seizures in rats Protective effect [263] Bicuculline-induced (rat prepiriform cortex) seizures Seizure protection [267] Bicuculline-induced (rat hippocampal slices) epileptiform activity Decreased epileptiform activity [168] 3-mercaptopropionic acid-induced (intraperitoneal injection) seizures in mice…”

Section: Ado Receptor Agonistsmentioning

confidence: 99%

“…Increased seizure latency [118] 3-nitropropionic acid-induced (intraperitoneal injection) seizures in mice Anticonvulsant effect [266] 2-CLA (A1 receptor agonist) Mg 2+ -free condition-induced (human neocortical slices) epileptiform activity Decreased/blocked epileptiform activity [219] Kindling (rat piriform cortex, hippocampus, and amygdala) model Anticonvulsant effect [273][274][275][276][277] Lithium-pilocarpine-induced status epilepticus in rats Protective effect [216] Pentylenetetrazole-induced (subcutane, and intraperitoneal injection) seizures in mice Protective effect [237] Pentylenetetrazole-induced (intraperitoneal injection) seizures in mice Increased seizure latency [118] Pentylenetetrazole-induced (intravenous application) seizures in rats Increased seizure threshold [265] Bicuculline-induced (rat prepiriform cortex) seizures Seizure protection [267] Bicuculline-induced (rat hippocampal slices) epileptiform activity Decreased epileptiform activity [168] Kainic acid-induced (intraperitoneal injection) seizures in mice Increased seizure latency [118] 3-mercaptopropionic acid-induced (intraperitoneal injection) seizures in mice Increased seizure latency [118] CHA (A1 receptor agonist)…”

Section: Ado Receptor Agonistsmentioning

confidence: 99%

“…Pentylenetetrazole-induced (intraperitoneal injection) seizures in mice Increased seizure latency [118] Penicillin-induced (rabbit cortex) epileptiform activity Prevents the spreading of the epileptic activity [106] Potassium-induced (rat hippocampal slices) epileptiform activity Blocked epileptiform bursting [280] Bicuculline-induced (rat hippocampal slices) epileptiform activity Decreased epileptiform activity [168] Kindling (rat amygdala, hippocampus, caudate nucleus) model Seizure reduction [119,272] Pilocarpine-induced seizures in rats Anticonvulsant effect [270] 3-mercaptopropionic acid-induced (intraperitoneal injection) seizures in mice…”

Section: Ado Receptor Agonistsmentioning

confidence: 99%

See 2 more Smart Citations

The Antiepileptic Potential of Nucleosides

Kovács¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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Despite newly developed antiepileptic drugs to suppress epileptic symptoms, approximately one third of patients remain drug refractory. Consequently, there is an urgent need to develop more effective therapeutic approaches to treat epilepsy. A great deal of evidence suggests that endogenous nucleosides, such as adenosine (Ado), guanosine (Guo), inosine (Ino) and uridine (Urd), participate in the regulation of pathomechanisms of epilepsy. Adenosine and its analogues, together with non-adenosine (non-Ado) nucleosides (e.g., Guo, Ino and Urd), have shown antiseizure activity. Adenosine kinase (ADK) inhibitors, Ado uptake inhibitors and Ado-releasing implants also have beneficial effects on epileptic seizures. These results suggest that nucleosides and their analogues, in addition to other modulators of the nucleoside system, could provide a new opportunity for the treatment of different types of epilepsies. Therefore, the aim of this review article is to summarize our present knowledge about the nucleoside system as a promising target in the treatment of epilepsy.

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Adenosine receptors in brain: Neuromodulation and role in epilepsy

Chin

1989

Annals of Neurology

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Adenosine is now recognized as an important endogenous modulator of neuronal excitability in the mammalian central nervous system. Adenosine is produced and released in the brain, where it exerts potent depressant effects on neuronal firing and synaptic transmission. Multiple adenosine receptor subtypes have been characterized using biochemical, electrophysiological, and radioligand binding techniques. Adenosine analogues have potent anticonvulsant actions in vitro and antagonize seizures in animals induced by a variety of mechanisms, including kindling. The future development of selective adenosine receptor agonists may provide new and more effective treatment for epilepsy.

show abstract

Adenosine inhibits epileptiform activity arising in hippocampal area CA3

Cited by 95 publications

References 56 publications

Transient and selective blockade of adenosine A1-receptors by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) causes sustained epileptiform activity in hippocampal CA3 neurons of guinea pigs

Transient and selective blockade of adenosine A1-receptors by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) causes sustained epileptiform activity in hippocampal CA3 neurons of guinea pigs

The Antiepileptic Potential of Nucleosides

Adenosine receptors in brain: Neuromodulation and role in epilepsy

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