Non-competitive regulation of phencyclidine/σ-receptors by the N-methyl-d-aspartate receptor antagonist d-(-)-2-amino-5-phosphonovaleric acid

Daniel C. Javitt; Alan Jotkowitz; Ratna Sircar; Stephen R. Zukin

doi:10.1016/0304-3940(87)90632-X

Non-competitive regulation of phencyclidine/σ-receptors by the N-methyl-d-aspartate receptor antagonist d-(-)-2-amino-5-phosphonovaleric acid

Daniel C. Javitt, Alan Jotkowitz, Ratna Sircar, Stephen R. Zukin

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

54 Scopus citations

Abstract

d-(-)-2-Amino-5-phosphonovaleric acid (d(-)AP5), a selective, potent competitive antagonist of N-methyl-d-aspartate (NMDA)-type excitatory amino acid receptors was used to investigate the relationship between NMDA receptors and phencyclidine (PCP) binding. Incubation of rat brain membranes with d(-)AP5 decreased the apparent number of PCP/σ-receptors in dose-dependent fashion without affecting their affinity for [2-thienyl-³H]cyclohexylpiperidine (TCP). These data, taken together with electrophysiological evidence that PCP non-competitively antagonizes NMDA receptor-mediated transmission, are consistent with the hypothesis that the PCP/σ-receptor may be situated in or near a channel regulated by an NMDA receptor complex.

Original language	English
Pages (from-to)	193-198
Number of pages	6
Journal	Neuroscience Letters
Volume	78
Issue number	2
DOIs	https://doi.org/10.1016/0304-3940(87)90632-X
State	Published - 22 Jul 1987
Externally published	Yes

Keywords

Excitatory amino acid
Glutamic acid
N-Methyl-d-aspartic acid
Phencyclidine
Receptor
Schizophrenia

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1016/0304-3940(87)90632-X

Cite this

@article{0fe13df7c998475ab158c7b28912c9b7,

title = "Non-competitive regulation of phencyclidine/σ-receptors by the N-methyl-d-aspartate receptor antagonist d-(-)-2-amino-5-phosphonovaleric acid",

abstract = "d-(-)-2-Amino-5-phosphonovaleric acid (d(-)AP5), a selective, potent competitive antagonist of N-methyl-d-aspartate (NMDA)-type excitatory amino acid receptors was used to investigate the relationship between NMDA receptors and phencyclidine (PCP) binding. Incubation of rat brain membranes with d(-)AP5 decreased the apparent number of PCP/σ-receptors in dose-dependent fashion without affecting their affinity for [2-thienyl-3H]cyclohexylpiperidine (TCP). These data, taken together with electrophysiological evidence that PCP non-competitively antagonizes NMDA receptor-mediated transmission, are consistent with the hypothesis that the PCP/σ-receptor may be situated in or near a channel regulated by an NMDA receptor complex.",

keywords = "Excitatory amino acid, Glutamic acid, N-Methyl-d-aspartic acid, Phencyclidine, Receptor, Schizophrenia",

author = "Javitt, {Daniel C.} and Alan Jotkowitz and Ratna Sircar and Zukin, {Stephen R.}",

year = "1987",

month = jul,

day = "22",

doi = "10.1016/0304-3940(87)90632-X",

language = "English",

volume = "78",

pages = "193--198",

journal = "Neuroscience Letters",

issn = "0304-3940",

publisher = "Elsevier Ireland Ltd",

number = "2",

}

TY - JOUR

T1 - Non-competitive regulation of phencyclidine/σ-receptors by the N-methyl-d-aspartate receptor antagonist d-(-)-2-amino-5-phosphonovaleric acid

AU - Javitt, Daniel C.

AU - Jotkowitz, Alan

AU - Sircar, Ratna

AU - Zukin, Stephen R.

PY - 1987/7/22

Y1 - 1987/7/22

N2 - d-(-)-2-Amino-5-phosphonovaleric acid (d(-)AP5), a selective, potent competitive antagonist of N-methyl-d-aspartate (NMDA)-type excitatory amino acid receptors was used to investigate the relationship between NMDA receptors and phencyclidine (PCP) binding. Incubation of rat brain membranes with d(-)AP5 decreased the apparent number of PCP/σ-receptors in dose-dependent fashion without affecting their affinity for [2-thienyl-3H]cyclohexylpiperidine (TCP). These data, taken together with electrophysiological evidence that PCP non-competitively antagonizes NMDA receptor-mediated transmission, are consistent with the hypothesis that the PCP/σ-receptor may be situated in or near a channel regulated by an NMDA receptor complex.

AB - d-(-)-2-Amino-5-phosphonovaleric acid (d(-)AP5), a selective, potent competitive antagonist of N-methyl-d-aspartate (NMDA)-type excitatory amino acid receptors was used to investigate the relationship between NMDA receptors and phencyclidine (PCP) binding. Incubation of rat brain membranes with d(-)AP5 decreased the apparent number of PCP/σ-receptors in dose-dependent fashion without affecting their affinity for [2-thienyl-3H]cyclohexylpiperidine (TCP). These data, taken together with electrophysiological evidence that PCP non-competitively antagonizes NMDA receptor-mediated transmission, are consistent with the hypothesis that the PCP/σ-receptor may be situated in or near a channel regulated by an NMDA receptor complex.

KW - Excitatory amino acid

KW - Glutamic acid

KW - N-Methyl-d-aspartic acid

KW - Phencyclidine

KW - Receptor

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=0023225289&partnerID=8YFLogxK

U2 - 10.1016/0304-3940(87)90632-X

DO - 10.1016/0304-3940(87)90632-X

M3 - Article

AN - SCOPUS:0023225289

SN - 0304-3940

VL - 78

SP - 193

EP - 198

JO - Neuroscience Letters

JF - Neuroscience Letters

IS - 2

ER -

Non-competitive regulation of phencyclidine/σ-receptors by the N-methyl-d-aspartate receptor antagonist d-(-)-2-amino-5-phosphonovaleric acid

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this