Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2008 Sep 30;10539:15118-23. doi: 10.1073/pnas.0807277105.
Show Gene links
Show Anatomy links
Adenosine receptor antagonists alter the stability of human epileptic GABAA receptors.
Roseti C
,
Martinello K
,
Fucile S
,
Piccari V
,
Mascia A
,
Di Gennaro G
,
Quarato PP
,
Manfredi M
,
Esposito V
,
Cantore G
,
Arcella A
,
Simonato M
,
Fredholm BB
,
Limatola C
,
Miledi R
,
Eusebi F
.
???displayArticle.abstract???
We examined how the endogenous anticonvulsant adenosine might influence gamma-aminobutyric acid type A (GABA(A)) receptor stability and which adenosine receptors (ARs) were involved. Upon repetitive activation (GABA 500 microM), GABA(A) receptors, microtransplanted into Xenopus oocytes from neurosurgically resected epileptic human nervous tissues, exhibited an obvious GABA(A)-current (I(GABA)) run-down, which was consistently and significantly reduced by treatment with the nonselective adenosine receptor antagonist CGS15943 (100 nM) or with adenosine deaminase (ADA) (1 units/ml), that inactivates adenosine. It was also found that selective antagonists of A2B (MRS1706, 10 nM) or A3 (MRS1334, 30 nM) receptors reduced I(GABA) run-down, whereas treatment with the specific A1 receptor antagonist DPCPX (10 nM) was ineffective. The selective A2A receptor antagonist SCH58261 (10 nM) reduced or potentiated I(GABA) run-down in approximately 40% and approximately 20% of tested oocytes, respectively. The ADA-resistant, AR agonist 2-chloroadenosine (2-CA) (10 microM) potentiated I(GABA) run-down but only in approximately 20% of tested oocytes. CGS15943 administration again decreased I(GABA) run-down in patch-clamped neurons from either human or rat neocortex slices. I(GABA) run-down in pyramidal neurons was equivalent in A1 receptor-deficient and wt neurons but much larger in neurons from A2A receptor-deficient mice, indicating that, in mouse cortex, GABA(A)-receptor stability is tonically influenced by A2A but not by A1 receptors. I(GABA) run-down from wt mice was not affected by 2-CA, suggesting maximal ARs activity by endogenous adenosine. Our findings strongly suggest that cortical A2-A3 receptors alter the stability of GABA(A) receptors, which could offer therapeutic opportunities.
Bahima,
Endogenous hemichannels play a role in the release of ATP from Xenopus oocytes.
2006, Pubmed,
Xenbase
Bahima,
Endogenous hemichannels play a role in the release of ATP from Xenopus oocytes.
2006,
Pubmed
,
Xenbase
Bell-Horner,
ERK/MAPK pathway regulates GABAA receptors.
2006,
Pubmed
Boison,
The adenosine kinase hypothesis of epileptogenesis.
2008,
Pubmed
Boison,
Adenosine as a neuromodulator in neurological diseases.
2008,
Pubmed
Chen,
A(2A) adenosine receptor deficiency attenuates brain injury induced by transient focal ischemia in mice.
1999,
Pubmed
Cherubini,
GABA: an excitatory transmitter in early postnatal life.
1991,
Pubmed
Ciruela,
Heterodimeric adenosine receptors: a device to regulate neurotransmitter release.
2006,
Pubmed
Cohen,
On the origin of interictal activity in human temporal lobe epilepsy in vitro.
2002,
Pubmed
Forghani,
Adenosine antagonists have differential effects on induction of long-term potentiation in hippocampal slices.
1995,
Pubmed
Fredholm,
Adenosine, an endogenous distress signal, modulates tissue damage and repair.
2007,
Pubmed
Fredholm,
International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors.
2001,
Pubmed
Goodkin,
GABA(A) receptor internalization during seizures.
2007,
Pubmed
Gourine,
Release of ATP in the central nervous system during systemic inflammation: real-time measurement in the hypothalamus of conscious rabbits.
2007,
Pubmed
Huberfeld,
Perturbed chloride homeostasis and GABAergic signaling in human temporal lobe epilepsy.
2007,
Pubmed
Jacobson,
Adenosine receptors as therapeutic targets.
2006,
Pubmed
Jankovic,
Are adenosine antagonists, such as istradefylline, caffeine, and chocolate, useful in the treatment of Parkinson's disease?
2008,
Pubmed
Johansson,
Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor.
2001,
Pubmed
Latini,
Adenosine in the central nervous system: release mechanisms and extracellular concentrations.
2001,
Pubmed
McDonald,
Adjacent phosphorylation sites on GABAA receptor beta subunits determine regulation by cAMP-dependent protein kinase.
1998,
Pubmed
McGaraughty,
Anticonvulsant and antinociceptive actions of novel adenosine kinase inhibitors.
2005,
Pubmed
Miledi,
Microtransplantation of neurotransmitter receptors from cells to Xenopus oocyte membranes: new procedure for ion channel studies.
2006,
Pubmed
,
Xenbase
Miledi,
A calcium-dependent transient outward current in Xenopus laevis oocytes.
1982,
Pubmed
,
Xenbase
Pagonopoulou,
Modulatory role of adenosine and its receptors in epilepsy: possible therapeutic approaches.
2006,
Pubmed
Palma,
BDNF modulates GABAA receptors microtransplanted from the human epileptic brain to Xenopus oocytes.
2005,
Pubmed
,
Xenbase
Palma,
Phosphatase inhibitors remove the run-down of gamma-aminobutyric acid type A receptors in the human epileptic brain.
2004,
Pubmed
,
Xenbase
Palma,
GABA(A)-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABA(A) "phasic" receptors.
2007,
Pubmed
,
Xenbase
Palma,
Abnormal GABAA receptors from the human epileptic hippocampal subiculum microtransplanted to Xenopus oocytes.
2005,
Pubmed
,
Xenbase
Ragozzino,
Rundown of GABA type A receptors is a dysfunction associated with human drug-resistant mesial temporal lobe epilepsy.
2005,
Pubmed
,
Xenbase
Ribeiro,
Adenosine receptors in the nervous system: pathophysiological implications.
2002,
Pubmed
Schock,
ATP release by way of connexin 36 hemichannels mediates ischemic tolerance in vitro.
2008,
Pubmed
Song,
Protein kinase C regulation of GABAA receptors.
2005,
Pubmed
