title: Pilocarpine-Induced Status Epilepticus Increases the Sensitivity of P2X7 and P2Y1 Receptors to Nucleotides at Neural Progenitor Cells of the Juvenile Rodent Hippocampus.
abstract: Patch-clamp recordings indicated the presence of P2X7 receptors at neural progenitor cells (NPCs) in the subgranular zone of the dentate gyrus in hippocampal brain slices prepared from transgenic nestin reporter mice. The activation of these receptors caused inward current near the resting membrane potential of the NPCs, while P2Y1 receptor activation initiated outward current near the reversal potential of the P2X7 receptor current. Both receptors were identified by biophysical/pharmacological methods. When the brain slices were prepared from mice which underwent a pilocarpine-induced status epilepticus or when brain slices were incubated in pilocarpine-containing external medium, the sensitivity of P2X7 and P2Y1 receptors was invariably increased. Confocal microscopy confirmed the localization of P2X7 and P2Y1 receptor-immunopositivity at nestin-positive NPCs. A one-time status epilepticus in rats caused after a latency of about 5 days recurrent epileptic fits. The blockade of central P2X7 receptors increased the number of seizures and their severity. It is hypothesized that P2Y1 receptors after a status epilepticus may increase the ATP-induced proliferation/ectopic migration of NPCs; the P2X7 receptor-mediated necrosis/apoptosis might counteract these effects, which would otherwise lead to a chronic manifestation of recurrent epileptic fits.
authors.affiliation: Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, 04107 Leipzig, Germany.
authors.forename: Katalin
authors.initials: K
authors.lastname: Rozmer
authors.affiliation: Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, 04107 Leipzig, Germany.|Department of Physiology, Shanghai Jiaotong University School of Medicine, 200025 Shanghai, China.
authors.forename: Po
authors.initials: P
authors.lastname: Gao
authors.affiliation: Disciplina de Neurociência, Departamento de Neurologia e Neurocirurgia da Universidade Federal de São Paulo, São Paulo/SP, Brazil.
authors.forename: Michelle G L
authors.initials: MGL
authors.lastname: Araújo
authors.affiliation: Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, 04107 Leipzig, Germany.
authors.forename: Muhammad Tahir
authors.initials: MT
authors.lastname: Khan
authors.affiliation: Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, 04107 Leipzig, Germany.|Acupuncture and Tuina School, Chengdu University of TCM, 610075 Chengdu, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Physiology, Shanghai Jiaotong University School of Medicine, 200025 Shanghai, China.
authors.forename: Weifang
authors.initials: W
authors.lastname: Rong
authors.affiliation: Acupuncture and Tuina School, Chengdu University of TCM, 610075 Chengdu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, 04107 Leipzig, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Franke
authors.affiliation: Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, 04107 Leipzig, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Krügel
authors.affiliation: Disciplina de Neurociência, Departamento de Neurologia e Neurocirurgia da Universidade Federal de São Paulo, São Paulo/SP, Brazil.
authors.forename: Maria José S
authors.initials: MJS
authors.lastname: Fernandes
authors.affiliation: Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, 04107 Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Illes
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018721:Muscarinic Agonists / Q000633:toxicity; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism; D009711:Nucleotides / Q000494:pharmacology*; D010862:Pilocarpine / Q000633:toxicity; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1 / Q000235:genetics / Q000378:metabolism*; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology*
chemical_list: C000602458:AZ10606120; D000634:Aminoquinolines; D018683:Excitatory Amino Acid Agents; D018721:Muscarinic Agonists; D009711:Nucleotides; D058920:Purinergic P2X Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D058472:Receptors, Purinergic P2Y1; C485184:enhanced green fluorescent protein; D010862:Pilocarpine; D049452:Green Fluorescent Proteins; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D000218:Adamantane
keywords: P2X7 receptors; P2Y1 receptors; neural progenitor cells; status epilepticus; subgranular zone