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Presynaptic inhibitory receptors mediate the depression of synaptic transmission upon hypoxia in rat hippocampal slices.

Abstract
Hypoxia markedly depresses synaptic transmission in hippocampal slices of the rat. This depression is attributed to presynaptic inhibition of glutamate release and is largely mediated by adenosine released during hypoxia acting through presynaptic adenosine A(1) receptors. Paired pulse facilitation studies allowed us to confirm the presynaptic nature of the depression of synaptic transmission during hypoxia. We tested the hypothesis that activation of heterosynaptic inhibitory receptors localized in glutamatergic presynaptic terminals in the hippocampus, namely gamma-aminobutyric acid subtype B (GABA(B)) receptors, alpha(2)-adrenergic receptors, and muscarinic receptors might contribute to the hypoxia-induced depression of synaptic transmission. Field excitatory postsynaptic potentials were recorded in the CA1 area of hippocampal slices from young adult (5-6 weeks) Wistar rats. Neither the selective antagonist for alpha(2)-adrenergic receptors, rauwolscine (10 microM), nor the antagonist for the GABA(B) receptors, CGP 55845 (10 microM), modified the response to hypoxia. The selective adenosine A(1) receptor antagonist, DPCPX (50 nM), reduced the hypoxia-induced depression of synaptic transmission to 59.2+/-9.6%, and the muscarinic receptor antagonist, atropine (10 microM), in the presence of DPCPX (50 nM), further attenuated the depression of synaptic transmission to 49.4+/-8.0%. In the same experimental conditions, in the presence of DPCPX (50 nM), the muscarinic M(2) receptor antagonist AF-DX 116 (10 microM), but not the M(1) receptor antagonist pirenzepine (1 microM), also attenuated the hypoxia-induced depression to 41.6+/-6.6%. Activation of muscarinic M(2) receptors contributes to the depression of synaptic transmission upon hypoxia. This effect should assume particular relevance during prolonged periods of hypoxia when other mechanisms may become less efficient.
AuthorsJ E Coelho, A de Mendonça, J A Ribeiro
JournalBrain research (Brain Res) Vol. 869 Issue 1-2 Pg. 158-65 (Jun 30 2000) ISSN: 0006-8993 [Print] Netherlands
PMID10865070 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Receptor, Muscarinic M2
  • Receptors, Adrenergic, alpha-2
  • Receptors, GABA-B
  • Receptors, Muscarinic
  • Glutamic Acid
Topics
  • Animals
  • Excitatory Postsynaptic Potentials (physiology)
  • Glutamic Acid (metabolism)
  • Hippocampus (drug effects, pathology, physiopathology)
  • Hypoxia (pathology, physiopathology)
  • In Vitro Techniques
  • Male
  • Neural Inhibition (drug effects, physiology)
  • Neurons (drug effects, metabolism, pathology)
  • Presynaptic Terminals (drug effects, metabolism, ultrastructure)
  • Rats
  • Rats, Wistar
  • Receptor, Muscarinic M2
  • Receptors, Adrenergic, alpha-2 (drug effects, metabolism)
  • Receptors, GABA-B (drug effects, metabolism)
  • Receptors, Muscarinic (drug effects, metabolism)
  • Synaptic Transmission (drug effects, physiology)

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