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Blockage of A2A and A3 adenosine receptors decreases the desensitization of human GABAA receptors microtransplanted to Xenopus oocytes

digela 添加于 2009-9-3 00:02 | 1976 次阅读 | 0 个评论

作者
Roseti C, Palma E, Martinello K, Fucile S, Morace R, Esposito V, Cantore G, Arcella A, Giangaspero F, Aronica E, Mascia A, Di Gennaro G, Quarato PP, Manfredi M, Cristalli G, Lambertucci C, Marucci G, Volpini R, Limatola C, Eusebi F
摘要
We previously found that the endogenous anticonvulsant adenosine, acting through A(2A) and A(3) adenosine receptors (ARs), alters the stability of currents (I(GABA)) generated by GABA(A) receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether ARs alter the stability (desensitization) of I(GABA) expressed in focal cortical dysplasia (FCD) and in periglioma epileptic tissues. The experiments were performed with tissues from 23 patients, using voltage-clamp recordings in Xenopus oocytes microinjected with membranes isolated from human MTLE and FCD tissues or using patch-clamp recordings of pyramidal neurons in epileptic tissue slices. On repetitive activation, the epileptic GABA(A) receptors revealed instability, manifested by a large I(GABA) rundown, which in most of the oocytes ( approximately 70%) was obviously impaired by the new A(2A) antagonists ANR82, ANR94, and ANR152. In most MTLE tissue-microtransplanted oocytes, a new A(3) receptor antagonist (ANR235) significantly improved I(GABA) stability. Moreover, patch-clamped pyramidal neurons from human neocortical slices of periglioma epileptic tissues exhibited altered I(GABA) rundown on ANR94 treatment. Our findings indicate that antagonizing A(2A) and A(3) receptors increases the I(GABA) stability in different epileptic tissues and suggest that adenosine derivatives may offer therapeutic opportunities in various forms of human epilepsy.
详细资料
- 文献种类:期刊
- 期刊名称: Proceedings of the National Academy of Sciences of the United States of America
- 期刊缩写: Proc Natl Acad Sci U S A
- 期卷页: 2009年
- 地址: Istituto Pasteur-Fondazione Cenci Bolognetti & Dipartimento di Fisiologia Umana e Farmacologia-Centro di Eccellenza BEMM, Universita' di Roma La Sapienza, I00185 Rome, Italy
- ISBN: 1091-6490
- 备注:PMID:19721003
标签

epilepsy
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