Identification of 5‐hydroxytryptamine1D binding sites in human brain membranes

Stephen J. Peroutka, Julie A. Switzer, Anne Hamik

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

High‐affinity, specific 3H‐5‐hydroxytryptamine (5‐HT) binding was analyzed in membrane homogenates of human frontal cortex, caudate, and globus pallidus. 5‐HT1A and 5‐HT1C binding sites were pharmacologically blocked using 100 nM 8‐hydroxy‐N,N‐dipropyl‐2‐aminotetralin (8‐OH‐DPAT) and 100 nM mesulergine, respectively. The majority of 5‐HT1 sites remained in each of the three brain regions under these conditions. The pattern of nucleotide interactions with these binding sites (GppNHp = GTP = GDP > GMP = adenine nucleotides) suggests a possible linkage to a G protein. RU 24969 competition studies confirmed the absence of 5‐HT1B binding sites in human cortex, caudate, and globus pallidus. Drug interactions with putative 5‐HT1D binding sites in bovine caudate membranes correlated significantly with their affinities for human membrane recognition sites labeled by 3H‐5‐HT in the presence of 100 nM 8‐OH‐DPAT + 100 nM mesulergine. We conclude that the majority of 3H‐5‐HT‐labeled recognition sites in human cortex, caudate, and globus pallidus represent 5‐HT1D binding sites.

Original languageEnglish (US)
Pages (from-to)61-66
Number of pages6
JournalSynapse
Volume3
Issue number1
DOIs
StatePublished - Jan 1 1989

Fingerprint

Binding Sites
Globus Pallidus
Membranes
Brain
Adenine Nucleotides
Frontal Lobe
Guanosine Triphosphate
Drug Interactions
GTP-Binding Proteins
Nucleotides
mesulergine

Keywords

  • GTP
  • H‐5‐HT
  • Receptors
  • Serotonin

Cite this

Identification of 5‐hydroxytryptamine1D binding sites in human brain membranes. / Peroutka, Stephen J.; Switzer, Julie A.; Hamik, Anne.

In: Synapse, Vol. 3, No. 1, 01.01.1989, p. 61-66.

Research output: Contribution to journalArticle

Peroutka, Stephen J. ; Switzer, Julie A. ; Hamik, Anne. / Identification of 5‐hydroxytryptamine1D binding sites in human brain membranes. In: Synapse. 1989 ; Vol. 3, No. 1. pp. 61-66.
@article{e958854fcc274f96a4d52333413dfd51,
title = "Identification of 5‐hydroxytryptamine1D binding sites in human brain membranes",
abstract = "High‐affinity, specific 3H‐5‐hydroxytryptamine (5‐HT) binding was analyzed in membrane homogenates of human frontal cortex, caudate, and globus pallidus. 5‐HT1A and 5‐HT1C binding sites were pharmacologically blocked using 100 nM 8‐hydroxy‐N,N‐dipropyl‐2‐aminotetralin (8‐OH‐DPAT) and 100 nM mesulergine, respectively. The majority of 5‐HT1 sites remained in each of the three brain regions under these conditions. The pattern of nucleotide interactions with these binding sites (GppNHp = GTP = GDP > GMP = adenine nucleotides) suggests a possible linkage to a G protein. RU 24969 competition studies confirmed the absence of 5‐HT1B binding sites in human cortex, caudate, and globus pallidus. Drug interactions with putative 5‐HT1D binding sites in bovine caudate membranes correlated significantly with their affinities for human membrane recognition sites labeled by 3H‐5‐HT in the presence of 100 nM 8‐OH‐DPAT + 100 nM mesulergine. We conclude that the majority of 3H‐5‐HT‐labeled recognition sites in human cortex, caudate, and globus pallidus represent 5‐HT1D binding sites.",
keywords = "GTP, H‐5‐HT, Receptors, Serotonin",
author = "Peroutka, {Stephen J.} and Switzer, {Julie A.} and Anne Hamik",
year = "1989",
month = "1",
day = "1",
doi = "10.1002/syn.890030109",
language = "English (US)",
volume = "3",
pages = "61--66",
journal = "Synapse",
issn = "0887-4476",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Identification of 5‐hydroxytryptamine1D binding sites in human brain membranes

AU - Peroutka, Stephen J.

AU - Switzer, Julie A.

AU - Hamik, Anne

PY - 1989/1/1

Y1 - 1989/1/1

N2 - High‐affinity, specific 3H‐5‐hydroxytryptamine (5‐HT) binding was analyzed in membrane homogenates of human frontal cortex, caudate, and globus pallidus. 5‐HT1A and 5‐HT1C binding sites were pharmacologically blocked using 100 nM 8‐hydroxy‐N,N‐dipropyl‐2‐aminotetralin (8‐OH‐DPAT) and 100 nM mesulergine, respectively. The majority of 5‐HT1 sites remained in each of the three brain regions under these conditions. The pattern of nucleotide interactions with these binding sites (GppNHp = GTP = GDP > GMP = adenine nucleotides) suggests a possible linkage to a G protein. RU 24969 competition studies confirmed the absence of 5‐HT1B binding sites in human cortex, caudate, and globus pallidus. Drug interactions with putative 5‐HT1D binding sites in bovine caudate membranes correlated significantly with their affinities for human membrane recognition sites labeled by 3H‐5‐HT in the presence of 100 nM 8‐OH‐DPAT + 100 nM mesulergine. We conclude that the majority of 3H‐5‐HT‐labeled recognition sites in human cortex, caudate, and globus pallidus represent 5‐HT1D binding sites.

AB - High‐affinity, specific 3H‐5‐hydroxytryptamine (5‐HT) binding was analyzed in membrane homogenates of human frontal cortex, caudate, and globus pallidus. 5‐HT1A and 5‐HT1C binding sites were pharmacologically blocked using 100 nM 8‐hydroxy‐N,N‐dipropyl‐2‐aminotetralin (8‐OH‐DPAT) and 100 nM mesulergine, respectively. The majority of 5‐HT1 sites remained in each of the three brain regions under these conditions. The pattern of nucleotide interactions with these binding sites (GppNHp = GTP = GDP > GMP = adenine nucleotides) suggests a possible linkage to a G protein. RU 24969 competition studies confirmed the absence of 5‐HT1B binding sites in human cortex, caudate, and globus pallidus. Drug interactions with putative 5‐HT1D binding sites in bovine caudate membranes correlated significantly with their affinities for human membrane recognition sites labeled by 3H‐5‐HT in the presence of 100 nM 8‐OH‐DPAT + 100 nM mesulergine. We conclude that the majority of 3H‐5‐HT‐labeled recognition sites in human cortex, caudate, and globus pallidus represent 5‐HT1D binding sites.

KW - GTP

KW - H‐5‐HT

KW - Receptors

KW - Serotonin

UR - http://www.scopus.com/inward/record.url?scp=0024476895&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024476895&partnerID=8YFLogxK

U2 - 10.1002/syn.890030109

DO - 10.1002/syn.890030109

M3 - Article

VL - 3

SP - 61

EP - 66

JO - Synapse

JF - Synapse

SN - 0887-4476

IS - 1

ER -