An endogenous ligand of the brain σ/PCP receptor antagonizes NMDA-induced neurotransmitter release

Stephen R. Zukin; R. Suzanne Zukin; Wylie Vale; Jean Rivier; Roxanne Nichtenhauser; Lawrence D. Snell; Kenneth M. Johnson

doi:10.1016/0006-8993(87)91499-5

An endogenous ligand of the brain σ/PCP receptor antagonizes NMDA-induced neurotransmitter release

Stephen R. Zukin, R. Suzanne Zukin, Wylie Vale, Jean Rivier, Roxanne Nichtenhauser, Lawrence D. Snell, Kenneth M. Johnson

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

The present study provides evidence for the presence of an endogenous ligand for the phencyclidine (PCP) receptor of mammalian brain. Partially purified bovine hippocampal extracts potently and dose dependently inhibit binding to PCP receptors of [³HN-(1[2-thienyl]-cyclohexyl)piperidine (TCP), a highly potent and specific ligand of PCP receptors. In addition to demonstrating PCP-like binding properties, the partially purified extract mimics biological actions of PCP upon neurotransmitter release. HPLC fractions active in the [³]TCP binding assay, by contrast to fractions inactive in the binding assay, potently elicited stimulation of spontaneous acetycholine and dopamine efflux and inhibited NMDA-stimulated release of acetylcholine and dopamine. The transmitter release assay provides validation of a PCP-like physiological activity exerted by bovine hippocampal extracts purified by HPLC.

Original language	English (US)
Pages (from-to)	84-89
Number of pages	6
Journal	Brain Research
Volume	416
Issue number	1
DOIs	https://doi.org/10.1016/0006-8993(87)91499-5
State	Published - Jul 21 1987
Externally published	Yes

Keywords

N-Methyl-d-aspartate
Neurotransmitter release
Phencyclidine receptor
Phenycyclidine
Sigma receptor

ASJC Scopus subject areas

Developmental Biology
Molecular Biology
Clinical Neurology
General Neuroscience

Access to Document

10.1016/0006-8993(87)91499-5

Cite this

@article{5bdc24b84c5a4c81a1a041df047bd7bc,

title = "An endogenous ligand of the brain σ/PCP receptor antagonizes NMDA-induced neurotransmitter release",

abstract = "The present study provides evidence for the presence of an endogenous ligand for the phencyclidine (PCP) receptor of mammalian brain. Partially purified bovine hippocampal extracts potently and dose dependently inhibit binding to PCP receptors of [3HN-(1[2-thienyl]-cyclohexyl)piperidine (TCP), a highly potent and specific ligand of PCP receptors. In addition to demonstrating PCP-like binding properties, the partially purified extract mimics biological actions of PCP upon neurotransmitter release. HPLC fractions active in the [3]TCP binding assay, by contrast to fractions inactive in the binding assay, potently elicited stimulation of spontaneous acetycholine and dopamine efflux and inhibited NMDA-stimulated release of acetylcholine and dopamine. The transmitter release assay provides validation of a PCP-like physiological activity exerted by bovine hippocampal extracts purified by HPLC.",

keywords = "N-Methyl-d-aspartate, Neurotransmitter release, Phencyclidine receptor, Phenycyclidine, Sigma receptor",

author = "Zukin, {Stephen R.} and {Suzanne Zukin}, R. and Wylie Vale and Jean Rivier and Roxanne Nichtenhauser and Snell, {Lawrence D.} and Johnson, {Kenneth M.}",

note = "Funding Information: This work was supportedin part by PHS Grants fromt heN ationaIln stituteo n DrugA buseD A03383 to S.R.Z., DA01843a nd DA00069t o R.S.Z. and DA02073t o K.M.J. and by the Departmenotf Psy-chiatryA, lbertE insteinC ollegeo f Medicine/Monte-fiore MedicalC enterH, ermanM . van Praag,M .D., Ph. D., Chairman.",

year = "1987",

month = jul,

day = "21",

doi = "10.1016/0006-8993(87)91499-5",

language = "English (US)",

volume = "416",

pages = "84--89",

journal = "Brain Research",

issn = "0006-8993",

publisher = "Elsevier",

number = "1",

}

TY - JOUR

T1 - An endogenous ligand of the brain σ/PCP receptor antagonizes NMDA-induced neurotransmitter release

AU - Zukin, Stephen R.

AU - Suzanne Zukin, R.

AU - Vale, Wylie

AU - Rivier, Jean

AU - Nichtenhauser, Roxanne

AU - Snell, Lawrence D.

AU - Johnson, Kenneth M.

N1 - Funding Information: This work was supportedin part by PHS Grants fromt heN ationaIln stituteo n DrugA buseD A03383 to S.R.Z., DA01843a nd DA00069t o R.S.Z. and DA02073t o K.M.J. and by the Departmenotf Psy-chiatryA, lbertE insteinC ollegeo f Medicine/Monte-fiore MedicalC enterH, ermanM . van Praag,M .D., Ph. D., Chairman.

PY - 1987/7/21

Y1 - 1987/7/21

N2 - The present study provides evidence for the presence of an endogenous ligand for the phencyclidine (PCP) receptor of mammalian brain. Partially purified bovine hippocampal extracts potently and dose dependently inhibit binding to PCP receptors of [3HN-(1[2-thienyl]-cyclohexyl)piperidine (TCP), a highly potent and specific ligand of PCP receptors. In addition to demonstrating PCP-like binding properties, the partially purified extract mimics biological actions of PCP upon neurotransmitter release. HPLC fractions active in the [3]TCP binding assay, by contrast to fractions inactive in the binding assay, potently elicited stimulation of spontaneous acetycholine and dopamine efflux and inhibited NMDA-stimulated release of acetylcholine and dopamine. The transmitter release assay provides validation of a PCP-like physiological activity exerted by bovine hippocampal extracts purified by HPLC.

AB - The present study provides evidence for the presence of an endogenous ligand for the phencyclidine (PCP) receptor of mammalian brain. Partially purified bovine hippocampal extracts potently and dose dependently inhibit binding to PCP receptors of [3HN-(1[2-thienyl]-cyclohexyl)piperidine (TCP), a highly potent and specific ligand of PCP receptors. In addition to demonstrating PCP-like binding properties, the partially purified extract mimics biological actions of PCP upon neurotransmitter release. HPLC fractions active in the [3]TCP binding assay, by contrast to fractions inactive in the binding assay, potently elicited stimulation of spontaneous acetycholine and dopamine efflux and inhibited NMDA-stimulated release of acetylcholine and dopamine. The transmitter release assay provides validation of a PCP-like physiological activity exerted by bovine hippocampal extracts purified by HPLC.

KW - N-Methyl-d-aspartate

KW - Neurotransmitter release

KW - Phencyclidine receptor

KW - Phenycyclidine

KW - Sigma receptor

UR - http://www.scopus.com/inward/record.url?scp=0023182848&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023182848&partnerID=8YFLogxK

U2 - 10.1016/0006-8993(87)91499-5

DO - 10.1016/0006-8993(87)91499-5

M3 - Article

C2 - 2887250

AN - SCOPUS:0023182848

SN - 0006-8993

VL - 416

SP - 84

EP - 89

JO - Brain Research

JF - Brain Research

IS - 1

ER -

An endogenous ligand of the brain σ/PCP receptor antagonizes NMDA-induced neurotransmitter release

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this