Adenosine triphosphate accelerates recovery from hypoxic/hypoglycemic perturbation of guinea pig hippocampal neurotransmission via a P2 receptor

Hideo Aihara, Susumu Fujiwara, Ikuko Mizuta, Hitoshi Tada, Takeshi Kanno, Hidetoshi Tozaki, Kaoru Nagai, Yukio Yajima, Kazuhide Inoue, Takeshi Kondoh, Yasuhiko Motooka, Tomoyuki Nishizaki

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22 Citations (Scopus)


The present study was designed to assess the effects of adenosine triphosphate (ATP) on hippocampal neurotransmissions under the normal and hypoxic/hypoglycemic conditions. ATP reversely depressed population spikes (PSs), which were monitored in the dentate gyrus of guinea pig hippocampal slices, in a dose-dependent manner at concentrations ranged from 0.1 μM to 1 mM. A similar depression was obtained with the P2 receptor agonist, α,β-methylene ATP (α,β-MeATP), and the effect was inhibited by the P2 receptor antagonists, suramin and PPADS. The inhibitory action of ATP or α,β-MeATP was inhibited by the γ-aminobutyric acidA (GABAA) receptor antagonist, bicuculline, but it was not affected by theophylline, a broad inhibitor of adenosine (P1) receptors, tetraethylammonium, a broad inhibitor of K+ channels, or ecto-protein kinase inhibitors. ATP or α,β-MeATP enhanced GABA release from guinea pig hippocampal slices, that was inhibited by deleting extracellular Ca2+ or in the presence of tetrodotoxin, while ATP had no effect on GABA release from cultured rat hippocampal astrocytes or postsynaptic GABA-gated channel currents in cultured rat hippocampal neurons. Twenty-minutes deprivation of glucose and oxygen from extracellular solution abolished PSs, the amplitude recovering to about 30% of basal levels 50 min after returning to normal conditions. ATP or α,β-MeATP accelerated the recovery after hypoxic/hypoglycemic insult (approximately 80% of basal levels). Adenosine diphosphate and adenosine monophosphate accelerated the recovery, but to a much lesser extent, and adenosine had no effect. The results of the present study thus suggest that ATP inhibits neuronal activity by enhancing neuronal GABA release via a P2 receptor, perhaps a P2X receptor, thereby protecting against hypoxic/hypoglycemic perturbation of hippocampal neurotransmission.

Original languageEnglish
Pages (from-to)31-37
Number of pages7
JournalBrain Research
Issue number1
Publication statusPublished - Oct 11 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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