Subtype-specificity of the presynaptic α2-adrenoceptors modulating hippocampal norepinephrine release in rat

J. P. Kiss, G. Zsilla, A. Mike, T. Zelles, E. Toth, A. Lajtha, E. Vízi

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

In vivo brain microdialysis and high-performance liquid chromatography with electrochemical detection were used to study the effect of different selective α2-antagonists on hippocampal norepinephrine (NE) release in freely moving awake rat. Systemic administration (0.5 mg/kg i.p.) of either the α2AD-antagonist BRL 44408 or the α-2BC-antagonist ARC 239 did not significantly change the basal release of NE. At a higher dose (5 mg/kg i.p.) ARC 239 was still ineffective, whereas BRL 44408 caused a significant increase of the extracellular level of NE. Similar results were obtained from in vitro perfusion experiments. Rat hippocampal slices were loaded with [3H]NE and the electrical stimulation-evoked release of [3H]NE was determined. The α2-antagonists were applied in a concentration range of 10-8 to 10-6 M. ARC 239 was ineffective, whereas BRL 44408 significantly increased the electrically induced release of [3H]NE. In agreement with the data of microdialysis and perfusion experiments. BRL 44408 displaced [3H]yohimbine from hippocampal and cortical membranes of rat brain with high affinity whereas ARC 239 was less effective. The pKi values of eight different α2-adrenergic compounds showed a very good correlation (r = 0.98, slope = 1.11 P <0.0001) in hippocampus and frontal cortex where the α2-adrenoceptors have been characterized as α2D-subtype. Our data indicate that hippocampal NE release in rat is regulated by α2D-adrenoceptors, a species variation of the human α2A-subtype.

Original languageEnglish
Pages (from-to)238-244
Number of pages7
JournalBrain Research
Volume674
Issue number2
DOIs
Publication statusPublished - Mar 20 1995

Fingerprint

Adrenergic Receptors
Norepinephrine
Microdialysis
Perfusion
Yohimbine
Brain
Frontal Lobe
Adrenergic Agents
Electric Stimulation
Hippocampus
High Pressure Liquid Chromatography
Membranes
AR-C239
BRL 44408

Keywords

  • ARC 239
  • BRL 44408
  • Hippocampus
  • Microdialysis
  • Norepinephrine release
  • Receptor binding
  • α-Adrenoceptor subtype

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Subtype-specificity of the presynaptic α2-adrenoceptors modulating hippocampal norepinephrine release in rat. / Kiss, J. P.; Zsilla, G.; Mike, A.; Zelles, T.; Toth, E.; Lajtha, A.; Vízi, E.

In: Brain Research, Vol. 674, No. 2, 20.03.1995, p. 238-244.

Research output: Contribution to journalArticle

@article{82fd53d2350648dba4ba95d4a4ed083b,
title = "Subtype-specificity of the presynaptic α2-adrenoceptors modulating hippocampal norepinephrine release in rat",
abstract = "In vivo brain microdialysis and high-performance liquid chromatography with electrochemical detection were used to study the effect of different selective α2-antagonists on hippocampal norepinephrine (NE) release in freely moving awake rat. Systemic administration (0.5 mg/kg i.p.) of either the α2AD-antagonist BRL 44408 or the α-2BC-antagonist ARC 239 did not significantly change the basal release of NE. At a higher dose (5 mg/kg i.p.) ARC 239 was still ineffective, whereas BRL 44408 caused a significant increase of the extracellular level of NE. Similar results were obtained from in vitro perfusion experiments. Rat hippocampal slices were loaded with [3H]NE and the electrical stimulation-evoked release of [3H]NE was determined. The α2-antagonists were applied in a concentration range of 10-8 to 10-6 M. ARC 239 was ineffective, whereas BRL 44408 significantly increased the electrically induced release of [3H]NE. In agreement with the data of microdialysis and perfusion experiments. BRL 44408 displaced [3H]yohimbine from hippocampal and cortical membranes of rat brain with high affinity whereas ARC 239 was less effective. The pKi values of eight different α2-adrenergic compounds showed a very good correlation (r = 0.98, slope = 1.11 P <0.0001) in hippocampus and frontal cortex where the α2-adrenoceptors have been characterized as α2D-subtype. Our data indicate that hippocampal NE release in rat is regulated by α2D-adrenoceptors, a species variation of the human α2A-subtype.",
keywords = "ARC 239, BRL 44408, Hippocampus, Microdialysis, Norepinephrine release, Receptor binding, α-Adrenoceptor subtype",
author = "Kiss, {J. P.} and G. Zsilla and A. Mike and T. Zelles and E. Toth and A. Lajtha and E. V{\'i}zi",
year = "1995",
month = "3",
day = "20",
doi = "10.1016/0006-8993(94)01447-P",
language = "English",
volume = "674",
pages = "238--244",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Subtype-specificity of the presynaptic α2-adrenoceptors modulating hippocampal norepinephrine release in rat

AU - Kiss, J. P.

AU - Zsilla, G.

AU - Mike, A.

AU - Zelles, T.

AU - Toth, E.

AU - Lajtha, A.

AU - Vízi, E.

PY - 1995/3/20

Y1 - 1995/3/20

N2 - In vivo brain microdialysis and high-performance liquid chromatography with electrochemical detection were used to study the effect of different selective α2-antagonists on hippocampal norepinephrine (NE) release in freely moving awake rat. Systemic administration (0.5 mg/kg i.p.) of either the α2AD-antagonist BRL 44408 or the α-2BC-antagonist ARC 239 did not significantly change the basal release of NE. At a higher dose (5 mg/kg i.p.) ARC 239 was still ineffective, whereas BRL 44408 caused a significant increase of the extracellular level of NE. Similar results were obtained from in vitro perfusion experiments. Rat hippocampal slices were loaded with [3H]NE and the electrical stimulation-evoked release of [3H]NE was determined. The α2-antagonists were applied in a concentration range of 10-8 to 10-6 M. ARC 239 was ineffective, whereas BRL 44408 significantly increased the electrically induced release of [3H]NE. In agreement with the data of microdialysis and perfusion experiments. BRL 44408 displaced [3H]yohimbine from hippocampal and cortical membranes of rat brain with high affinity whereas ARC 239 was less effective. The pKi values of eight different α2-adrenergic compounds showed a very good correlation (r = 0.98, slope = 1.11 P <0.0001) in hippocampus and frontal cortex where the α2-adrenoceptors have been characterized as α2D-subtype. Our data indicate that hippocampal NE release in rat is regulated by α2D-adrenoceptors, a species variation of the human α2A-subtype.

AB - In vivo brain microdialysis and high-performance liquid chromatography with electrochemical detection were used to study the effect of different selective α2-antagonists on hippocampal norepinephrine (NE) release in freely moving awake rat. Systemic administration (0.5 mg/kg i.p.) of either the α2AD-antagonist BRL 44408 or the α-2BC-antagonist ARC 239 did not significantly change the basal release of NE. At a higher dose (5 mg/kg i.p.) ARC 239 was still ineffective, whereas BRL 44408 caused a significant increase of the extracellular level of NE. Similar results were obtained from in vitro perfusion experiments. Rat hippocampal slices were loaded with [3H]NE and the electrical stimulation-evoked release of [3H]NE was determined. The α2-antagonists were applied in a concentration range of 10-8 to 10-6 M. ARC 239 was ineffective, whereas BRL 44408 significantly increased the electrically induced release of [3H]NE. In agreement with the data of microdialysis and perfusion experiments. BRL 44408 displaced [3H]yohimbine from hippocampal and cortical membranes of rat brain with high affinity whereas ARC 239 was less effective. The pKi values of eight different α2-adrenergic compounds showed a very good correlation (r = 0.98, slope = 1.11 P <0.0001) in hippocampus and frontal cortex where the α2-adrenoceptors have been characterized as α2D-subtype. Our data indicate that hippocampal NE release in rat is regulated by α2D-adrenoceptors, a species variation of the human α2A-subtype.

KW - ARC 239

KW - BRL 44408

KW - Hippocampus

KW - Microdialysis

KW - Norepinephrine release

KW - Receptor binding

KW - α-Adrenoceptor subtype

UR - http://www.scopus.com/inward/record.url?scp=0028986495&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028986495&partnerID=8YFLogxK

U2 - 10.1016/0006-8993(94)01447-P

DO - 10.1016/0006-8993(94)01447-P

M3 - Article

C2 - 7796102

AN - SCOPUS:0028986495

VL - 674

SP - 238

EP - 244

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 2

ER -