Blockage of A(2A) and A(3) adenosine receptors decreases the desensitization of human GABA(A) receptors microtransplanted to Xenopus oocytes
| Autor: | Mario Manfredi, Eleonora Aronica, Giancarlo Di Gennaro, Gloria Cristalli, Sergio Fucile, Cristina Roseti, Addolorata Mascia, Vincenzo Esposito, Pier Paolo Quarato, Katiuscia Martinello, Roberta Morace, Felice Giangaspero, Antonietta Arcella, Fabrizio Eusebi, Catia Lambertucci, Eleonora Palma, Gabriella Marucci, Gianpaolo Cantore, Cristina Limatola, Rosaria Volpini |
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| Přispěvatelé: | ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Neurology, Pathology |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Patch-Clamp Techniques Receptor Adenosine A2A medicine.drug_class Adenosine A3 Receptor Antagonists Biology In Vitro Techniques Xenopus laevis Internal medicine medicine Animals Humans Patch clamp Receptor Multidisciplinary GABAA receptor Adenine Pyramidal Cells Receptor Adenosine A3 Cortical dysplasia Biological Sciences Receptor antagonist medicine.disease Receptors GABA-A Adenosine Adenosine receptor Cell biology Adenosine A2 Receptor Antagonists Malformations of Cortical Development Endocrinology Epilepsy Temporal Lobe nervous system epilepsy focal cortical dysplasia Oocytes Female medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, 106(37), 15927-15931. National Academy of Sciences |
| ISSN: | 0027-8424 |
| Popis: | 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 (≈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. |
| Databáze: | OpenAIRE |
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