Blockage of A 2A and A 3 adenosine receptors decreases the desensitization of human GABA A receptors microtransplanted to Xenopus oocytes
Year: 2009
Type: article
Abstract: 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.
Authors: Cristina Roseti, Eleonora Palma, Katiuscia Martinello, Sergio Fucile, Roberta Morace, Vincenzo Esposito, Gianpaolo Cantore, Antonietta Arcella, Felice Giangaspero, Eleonora Aronica, Addolorata Mascia, Giancarlo Di Gennaro, Pier Paolo Quarato, Mario Manfredi, Gloria Cristalli, Catia Lambertucci, Gabriella Marucci, Rosaria Volpini, Cristina Limatola, Fabrizio Eusebi
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1998786177