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

K Hoehn, CG Craig and TD White

Department of Pharmacology, Dalhousie University, 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.

Volume 255, Issue 1, pp. 174-181, 10/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				B. B. Fredholm, A. P. IJzerman, K. A. Jacobson, K.-N. Klotz, and J. Linden International Union of Pharmacology. XXV. Nomenclature and Classification of Adenosine Receptors Pharmacol. Rev., December 1, 2001; 53(4): 527 - 552. [Abstract] [Full Text] [PDF]

				Y. Wang and T. D. White Effect of Protein Kinase C Activation on N-Methyl-D-Aspartate-Evoked Release of Adenosine and [3H]Norepinephrine from Rat Cortical Slices J. Pharmacol. Exp. Ther., April 1, 1998; 285(1): 105 - 109. [Abstract] [Full Text]