Characterization of N-methyl-D-aspartate evoked striatal neurotransmitter release and its inhibition by phencyclidine-like drugs

L. D. Snell, K. M. Johnson

Research output: Contribution to journalArticle

Abstract

The excitatory amino acid L-glutamate (GLU) is known to increase the release of both 3H-acetylcholine (ACh) and 3H-dopamine (DA) from superfused rat striatal slices. N-methyl-D-aspartate (NMDA), the prototypic agonist at one of the glutamate receptor subclasses, evokes the release of DA and ACh via a mechanism which can be antagonized by phencyclidine (PCP). NMDA-evoked ACh release is reduced 80% by 1.2 mM MgCl2 while DA release is 50% reduced. In Ca+2-free buffer, NMDA-evoked ACh release is depressed to baseline levels while DA release is not. Tetrodotoxin (TTX) blocks NMDA-evoked ACh release, indicative of a somatic site of action. NMDA-induced DA release is insensitive to TTX, consistent with an action on striatal DA terminals. Other drugs with PCP-like activity inhibit NMDA-evoked striatal ACh and DA release with a rank-order potency and stereoselectivity similar to their rank-order potency in affecting several behavioral measures. These agents were approximately 10-fold more potent as antagonists of ACh release than DA release. The log-dose response curve of NMDA-induced ACh release was shifted 5-fold to the right in a non-parallel manner by 0.1 μM PCP. PCP (1 μM) was able to antagonize ACh release evoked by 1 mM GLU but was ineffective against that induced by equal concentrations of kainate and quisqualate, antagonists for other glutamate receptor subtypes.

Original languageEnglish (US)
JournalFederation Proceedings
Volume44
Issue number5
StatePublished - 1985

Fingerprint

Corpus Striatum
Phencyclidine
N-Methylaspartate
Acetylcholine
Neurotransmitter Agents
Dopamine
Pharmaceutical Preparations
Tetrodotoxin
Glutamic Acid
Quisqualic Acid
Excitatory Amino Acid Antagonists
Excitatory Amino Acids
Magnesium Chloride
Kainic Acid
Glutamate Receptors
Buffers

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Characterization of N-methyl-D-aspartate evoked striatal neurotransmitter release and its inhibition by phencyclidine-like drugs. / Snell, L. D.; Johnson, K. M.

In: Federation Proceedings, Vol. 44, No. 5, 1985.

Research output: Contribution to journalArticle

@article{537aec041f53476a9f51b2eee942bbbf,
title = "Characterization of N-methyl-D-aspartate evoked striatal neurotransmitter release and its inhibition by phencyclidine-like drugs",
abstract = "The excitatory amino acid L-glutamate (GLU) is known to increase the release of both 3H-acetylcholine (ACh) and 3H-dopamine (DA) from superfused rat striatal slices. N-methyl-D-aspartate (NMDA), the prototypic agonist at one of the glutamate receptor subclasses, evokes the release of DA and ACh via a mechanism which can be antagonized by phencyclidine (PCP). NMDA-evoked ACh release is reduced 80{\%} by 1.2 mM MgCl2 while DA release is 50{\%} reduced. In Ca+2-free buffer, NMDA-evoked ACh release is depressed to baseline levels while DA release is not. Tetrodotoxin (TTX) blocks NMDA-evoked ACh release, indicative of a somatic site of action. NMDA-induced DA release is insensitive to TTX, consistent with an action on striatal DA terminals. Other drugs with PCP-like activity inhibit NMDA-evoked striatal ACh and DA release with a rank-order potency and stereoselectivity similar to their rank-order potency in affecting several behavioral measures. These agents were approximately 10-fold more potent as antagonists of ACh release than DA release. The log-dose response curve of NMDA-induced ACh release was shifted 5-fold to the right in a non-parallel manner by 0.1 μM PCP. PCP (1 μM) was able to antagonize ACh release evoked by 1 mM GLU but was ineffective against that induced by equal concentrations of kainate and quisqualate, antagonists for other glutamate receptor subtypes.",
author = "Snell, {L. D.} and Johnson, {K. M.}",
year = "1985",
language = "English (US)",
volume = "44",
journal = "Federation Proceedings",
issn = "0014-9446",
number = "5",

}

TY - JOUR

T1 - Characterization of N-methyl-D-aspartate evoked striatal neurotransmitter release and its inhibition by phencyclidine-like drugs

AU - Snell, L. D.

AU - Johnson, K. M.

PY - 1985

Y1 - 1985

N2 - The excitatory amino acid L-glutamate (GLU) is known to increase the release of both 3H-acetylcholine (ACh) and 3H-dopamine (DA) from superfused rat striatal slices. N-methyl-D-aspartate (NMDA), the prototypic agonist at one of the glutamate receptor subclasses, evokes the release of DA and ACh via a mechanism which can be antagonized by phencyclidine (PCP). NMDA-evoked ACh release is reduced 80% by 1.2 mM MgCl2 while DA release is 50% reduced. In Ca+2-free buffer, NMDA-evoked ACh release is depressed to baseline levels while DA release is not. Tetrodotoxin (TTX) blocks NMDA-evoked ACh release, indicative of a somatic site of action. NMDA-induced DA release is insensitive to TTX, consistent with an action on striatal DA terminals. Other drugs with PCP-like activity inhibit NMDA-evoked striatal ACh and DA release with a rank-order potency and stereoselectivity similar to their rank-order potency in affecting several behavioral measures. These agents were approximately 10-fold more potent as antagonists of ACh release than DA release. The log-dose response curve of NMDA-induced ACh release was shifted 5-fold to the right in a non-parallel manner by 0.1 μM PCP. PCP (1 μM) was able to antagonize ACh release evoked by 1 mM GLU but was ineffective against that induced by equal concentrations of kainate and quisqualate, antagonists for other glutamate receptor subtypes.

AB - The excitatory amino acid L-glutamate (GLU) is known to increase the release of both 3H-acetylcholine (ACh) and 3H-dopamine (DA) from superfused rat striatal slices. N-methyl-D-aspartate (NMDA), the prototypic agonist at one of the glutamate receptor subclasses, evokes the release of DA and ACh via a mechanism which can be antagonized by phencyclidine (PCP). NMDA-evoked ACh release is reduced 80% by 1.2 mM MgCl2 while DA release is 50% reduced. In Ca+2-free buffer, NMDA-evoked ACh release is depressed to baseline levels while DA release is not. Tetrodotoxin (TTX) blocks NMDA-evoked ACh release, indicative of a somatic site of action. NMDA-induced DA release is insensitive to TTX, consistent with an action on striatal DA terminals. Other drugs with PCP-like activity inhibit NMDA-evoked striatal ACh and DA release with a rank-order potency and stereoselectivity similar to their rank-order potency in affecting several behavioral measures. These agents were approximately 10-fold more potent as antagonists of ACh release than DA release. The log-dose response curve of NMDA-induced ACh release was shifted 5-fold to the right in a non-parallel manner by 0.1 μM PCP. PCP (1 μM) was able to antagonize ACh release evoked by 1 mM GLU but was ineffective against that induced by equal concentrations of kainate and quisqualate, antagonists for other glutamate receptor subtypes.

UR - http://www.scopus.com/inward/record.url?scp=0021985081&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021985081&partnerID=8YFLogxK

M3 - Article

VL - 44

JO - Federation Proceedings

JF - Federation Proceedings

SN - 0014-9446

IS - 5

ER -