N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors regulating hippocampal norepinephrine release. II. Evidence for functional cooperation and for coexistence on the same axon terminal.

Article date: 1992/1/1

PubMed ID: 1370541

Journal name: The Journal of pharmacology and experimental therapeutics (ISSN: 0022-3565)


The possible interactions between activation of N-methyl-D-aspartic acid (NMDA) receptors and non-NMDA receptors regulating the release of [3H]norepinephrine [( 3H]NE) have been investigated in superfused synaptosomes from rat hippocampus. NMDA–at a concentration (100 microM) which, in a medium containing 1.2 mM Mg++ ions, did not evoke [3H]NE release–acquired releasing activity in the presence of equimolar concentrations of quisqualic acid (QA), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or kainic acid. The [3H] NE release evoked by NMDA plus QA in the presence of Mg++ ions was Ca(++)-dependent, partly tetrodotoxin-sensitive, inhibited by clonidine but insensitive to desipramine. The NMDA receptor antagonists D-2-amino-5-phosphonopentanoic acid (D-AP5) and (+)-5-methyl-10,11-dihydro-5-H-dibenzo[a,d]cycloepten-5,10-imine (MK-801) antagonized the NMDA-induced [3H]NE release in Mg(++)-free medium; the IC50 values amounted, respectively, to 81.4 microM and to 1.11 microM. When NMDA was tested in the presence of QA and Mg++ ions, the affinity of D-AP5 was enormously increased (IC50 = 40 nM; i.e., more than 6 orders of magnitude); the affinity of MK-801 was found to be augmented by 350-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Author List: Raiteri M, Garrone B, Pittaluga A

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Receptors, AMPA; Receptors, Amino Acid; Receptors, Cell Surface; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter; Ibotenic Acid; N-Methylaspartate; Dizocilpine Maleate; 2-Amino-5-phosphonovalerate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Quisqualic Acid; Magnesium; Norepinephrine;

Mesh terms: 2-Amino-5-phosphonovalerate/pharmacology; Animals; Axons/ultrastructure; Dizocilpine Maleate/pharmacology; Drug Interactions; Hippocampus/secretion; Ibotenic Acid/analogs & derivatives; Magnesium/pharmacology; Male; N-Methylaspartate/pharmacology; Norepinephrine/secretion; Quisqualic Acid/pharmacology; Rats; Rats, Inbred Strains; Receptors, AMPA; Receptors, Amino Acid; Receptors, Cell Surface/drug effects; Receptors, N-Methyl-D-Aspartate/physiology; Receptors, Neurotransmitter/physiology; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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