We previously found that the endogenous anticonvulsant adenosine, acting through A(2A) and A(3) adenosine receptors (ARs), alters the stability of currents (IGABA) generated by GABA(A) receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether ARs alter the stability (desensitization) of IGABA 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 (approximate to 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.

Blockage of A(2A) and A(3) adenosine receptors decreases the desensitization of human GABA(A) receptors microtransplanted to Xenopus oocytes / Roseti, Cristina; Palma, Eleonora; K., Martinello; Fucile, Sergio; R., Morace; Esposito, Vincenzo; Cantore, Giampaolo; A., Arcella; Giangaspero, Felice; E., Aronica; A., Mascia; G., Di Gennaro; P. P., Quarato; M., Manfredi; G., Cristalli; C., Lambertucci; G., Marucci; R., Volpini; Limatola, Cristina; Eusebi, Fabrizio. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 106:37(2009), pp. 15927-15931. [10.1073/pnas.0907324106]

Blockage of A(2A) and A(3) adenosine receptors decreases the desensitization of human GABA(A) receptors microtransplanted to Xenopus oocytes

ROSETI, CRISTINA;PALMA, Eleonora;FUCILE, Sergio;ESPOSITO, Vincenzo;CANTORE, Giampaolo;GIANGASPERO, FELICE;LIMATOLA, Cristina;EUSEBI, Fabrizio
2009

Abstract

We previously found that the endogenous anticonvulsant adenosine, acting through A(2A) and A(3) adenosine receptors (ARs), alters the stability of currents (IGABA) generated by GABA(A) receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether ARs alter the stability (desensitization) of IGABA 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 (approximate to 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.
epilepsy; focal cortical dysplasia
01 Pubblicazione su rivista::01a Articolo in rivista
Blockage of A(2A) and A(3) adenosine receptors decreases the desensitization of human GABA(A) receptors microtransplanted to Xenopus oocytes / Roseti, Cristina; Palma, Eleonora; K., Martinello; Fucile, Sergio; R., Morace; Esposito, Vincenzo; Cantore, Giampaolo; A., Arcella; Giangaspero, Felice; E., Aronica; A., Mascia; G., Di Gennaro; P. P., Quarato; M., Manfredi; G., Cristalli; C., Lambertucci; G., Marucci; R., Volpini; Limatola, Cristina; Eusebi, Fabrizio. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 106:37(2009), pp. 15927-15931. [10.1073/pnas.0907324106]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/229063
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 21
  • ???jsp.display-item.citation.isi??? 20
social impact