A comparison of N-methyl-D-aspartate-evoked release of adenosine and [3H]norepinephrine from rat cortical slices

K. Hoehn, C. G. Craig, T. D. White

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48 Citations (Scopus)

Résumé

Tetrodotoxin reduced N-methyl-D-aspartate (NMDA)-evoked release of adenosine by 35% but virtually abolished [3H]norepinephrine release. Although [3H]norepinephrine release from rat cortical slices evoked by 500 μM NMDA was abolished by 1.2 nM Mg++, which produces a voltage-sensitive, uncompetitive block of NMDA-channels, adenosine release was increased in the presence of Mg++. Partial depolarization with 12 mM K+ relieved the Mg++ block of 500 μM NMDA-evoked [3H]norepinephrine release but did not affect adenosine release, indicating that a Mg++ requirement for the adenosine release process per se cannot account for this discrepancy. NMDA was 33 times more potent in releasing adenosine than [3H]norepinephrine. At submaximal concentrations of NMD (10 and 20 μM), adenosine release was augmented in Mg++-free medium. Although a high concentration of the uncompetitive NMDA antagonist MK-801 [(+)5-methyl-10,11,dihydro-5H-dibenzo[a,d]cyclohepten-5-10-imine maleate] (3 μM) blocked NMDA-evoked release of [3H] norepinephrine and adenosine, a lower concentration (300 nM) decreased NMDA-evoked [3H]norepinephrine release by 66% without affecting adenosine release. These findings suggest that maximal adenosine release occurs when relatively few NMDA receptors are activated, raising the possibility that spare receptors exist for NMDA-evoked adenosine release. Rather than acting as a protectant against excessive NMDA excitation, released adenosine might provide an inhibitory threshold which must be overcome for NMDA-mediated neurotransmission to proceed.

Langue d'origineEnglish
Pages (de-à)174-181
Nombre de pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume255
Numéro de publication1
Statut de publicationPublished - 1990

ASJC Scopus Subject Areas

  • Molecular Medicine
  • Pharmacology

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