A comparison of N-methyl-D-aspartate-evoked release of adenosine and ( sup 3 H)norepinephrine from rat cortical slices

Journal Article · Mon Oct 01 00:00:00 EDT 1990 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:6217612

Hoehn, K; Craig, C G; White, T D ^[1]

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1. Dalhousie Univ., Halifax, Nova Scotia (Canada)

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 microM NMDA was abolished by 1.2 mM 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 microM 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 NMDA (10 and 20 microM), 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 microM) 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.

• OSTI ID: 6217612
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Vol. 255:1; ISSN 0022-3565
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ADENOSINE
SECRETION
ASPARTIC ACID
BIOCHEMICAL REACTION KINETICS
NORADRENALINE
CEREBRAL CORTEX
DOSE-RESPONSE RELATIONSHIPS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
AMINO ACIDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
BRAIN
CARBOXYLIC ACIDS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CEREBRUM
DRUGS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
REACTION KINETICS
RIBOSIDES
RODENTS
SYMPATHOMIMETICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques