Alterations in cardiac autonomic receptors following 6-hydroxydopamine treatment in rats

S. Yamada, H. I. Yamamura, W. R. Roeske

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

To characterize the regional changes in β-adrenergic and muscarinic cholinergic receptors in rat hearts following 6-hydroxydopamine (6-OHDA) treatment, receptor binding assys, using the specific ligands [3H]dihydroalprenolol (DHA) β-adrenergic receptor) and [3H]quinuclidinyl benzilate (QNB) (muscarinic cholinergic receptor) were performed in five regions of control and treated hearts. In addition, norepinephrine (NE) concentration and choline acetyltransferase activity in hearts were assayed to characterize the model. Rats were treated with 2 x 50 mg/kg i.v. injections of 6-OHDA.HBr at 24-h intervals and the hearts were removed 1,2, and 3 weeks later. The specific [3H]DHA binding was significantly higher in the ventricles and intraventricular septum than in the right atria of control rat hearts, suggesting a regional variation for β-adrenergic receptors. Following 6-OHDA treatment, the specific [3H]DHA binding to right atria, left ventricles, and ventricular septae significantly increased compared to similar regions of control rat hearts. The B(max) value in left ventricles was significantly increased, by 32, 38, and 17%, respectively, at 1, 2, and 3 weeks without a change in the K(d), suggesting an increase in the density of β-adrenergic receptors. There was a marked (60-80%) reduction of NE levels in all regions of 6-OHDA-treated rat hearts. These results suggest a relationship between the reduction of endogenous NE and the development of the increased density of β-adrenergic receptors in the rat hearts following 6-OHDA treatment. Specific [3H]QNB binding was significantly higher in atria than in ventricles of control rat hearts. The binding to each region was unchanged at 1 and 2 weeks following 6-OHDA treatment, while it was significantly increased in most regions at 3 weeks. There was a 30% increase in the B(max) in right and left atria without a change in the K(d), suggesting a change in the receptor density. The choline acetyltransferase activity was not significantly altered in any region of 60OHDA-treated rat hearts. The present study has demonstrated that destruction of noradrenergic nerve terminals in rats with 6-OHDA leads to an increase in the density of β-adrenergic receptors and a decrease in the NE concentration and that most of the cardiac muscarinic cholinergic receptors are not located on adrenergic neurons.

Original languageEnglish (US)
Pages (from-to)185-192
Number of pages8
JournalMolecular Pharmacology
Volume18
Issue number2
StatePublished - 1980
Externally publishedYes

Fingerprint

Oxidopamine
Adrenergic Receptors
Heart Atria
Norepinephrine
Cholinergic Receptors
Muscarinic Receptors
Dihydroalprenolol
Quinuclidinyl Benzilate
Therapeutics
Choline O-Acetyltransferase
Heart Ventricles
Adrenergic Neurons
Adrenergic Agents
Ligands
Injections

ASJC Scopus subject areas

  • Pharmacology

Cite this

Alterations in cardiac autonomic receptors following 6-hydroxydopamine treatment in rats. / Yamada, S.; Yamamura, H. I.; Roeske, W. R.

In: Molecular Pharmacology, Vol. 18, No. 2, 1980, p. 185-192.

Research output: Contribution to journalArticle

@article{3fbb9782ec504af694872080e74add12,
title = "Alterations in cardiac autonomic receptors following 6-hydroxydopamine treatment in rats",
abstract = "To characterize the regional changes in β-adrenergic and muscarinic cholinergic receptors in rat hearts following 6-hydroxydopamine (6-OHDA) treatment, receptor binding assys, using the specific ligands [3H]dihydroalprenolol (DHA) β-adrenergic receptor) and [3H]quinuclidinyl benzilate (QNB) (muscarinic cholinergic receptor) were performed in five regions of control and treated hearts. In addition, norepinephrine (NE) concentration and choline acetyltransferase activity in hearts were assayed to characterize the model. Rats were treated with 2 x 50 mg/kg i.v. injections of 6-OHDA.HBr at 24-h intervals and the hearts were removed 1,2, and 3 weeks later. The specific [3H]DHA binding was significantly higher in the ventricles and intraventricular septum than in the right atria of control rat hearts, suggesting a regional variation for β-adrenergic receptors. Following 6-OHDA treatment, the specific [3H]DHA binding to right atria, left ventricles, and ventricular septae significantly increased compared to similar regions of control rat hearts. The B(max) value in left ventricles was significantly increased, by 32, 38, and 17{\%}, respectively, at 1, 2, and 3 weeks without a change in the K(d), suggesting an increase in the density of β-adrenergic receptors. There was a marked (60-80{\%}) reduction of NE levels in all regions of 6-OHDA-treated rat hearts. These results suggest a relationship between the reduction of endogenous NE and the development of the increased density of β-adrenergic receptors in the rat hearts following 6-OHDA treatment. Specific [3H]QNB binding was significantly higher in atria than in ventricles of control rat hearts. The binding to each region was unchanged at 1 and 2 weeks following 6-OHDA treatment, while it was significantly increased in most regions at 3 weeks. There was a 30{\%} increase in the B(max) in right and left atria without a change in the K(d), suggesting a change in the receptor density. The choline acetyltransferase activity was not significantly altered in any region of 60OHDA-treated rat hearts. The present study has demonstrated that destruction of noradrenergic nerve terminals in rats with 6-OHDA leads to an increase in the density of β-adrenergic receptors and a decrease in the NE concentration and that most of the cardiac muscarinic cholinergic receptors are not located on adrenergic neurons.",
author = "S. Yamada and Yamamura, {H. I.} and Roeske, {W. R.}",
year = "1980",
language = "English (US)",
volume = "18",
pages = "185--192",
journal = "Molecular Pharmacology",
issn = "0026-895X",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - Alterations in cardiac autonomic receptors following 6-hydroxydopamine treatment in rats

AU - Yamada, S.

AU - Yamamura, H. I.

AU - Roeske, W. R.

PY - 1980

Y1 - 1980

N2 - To characterize the regional changes in β-adrenergic and muscarinic cholinergic receptors in rat hearts following 6-hydroxydopamine (6-OHDA) treatment, receptor binding assys, using the specific ligands [3H]dihydroalprenolol (DHA) β-adrenergic receptor) and [3H]quinuclidinyl benzilate (QNB) (muscarinic cholinergic receptor) were performed in five regions of control and treated hearts. In addition, norepinephrine (NE) concentration and choline acetyltransferase activity in hearts were assayed to characterize the model. Rats were treated with 2 x 50 mg/kg i.v. injections of 6-OHDA.HBr at 24-h intervals and the hearts were removed 1,2, and 3 weeks later. The specific [3H]DHA binding was significantly higher in the ventricles and intraventricular septum than in the right atria of control rat hearts, suggesting a regional variation for β-adrenergic receptors. Following 6-OHDA treatment, the specific [3H]DHA binding to right atria, left ventricles, and ventricular septae significantly increased compared to similar regions of control rat hearts. The B(max) value in left ventricles was significantly increased, by 32, 38, and 17%, respectively, at 1, 2, and 3 weeks without a change in the K(d), suggesting an increase in the density of β-adrenergic receptors. There was a marked (60-80%) reduction of NE levels in all regions of 6-OHDA-treated rat hearts. These results suggest a relationship between the reduction of endogenous NE and the development of the increased density of β-adrenergic receptors in the rat hearts following 6-OHDA treatment. Specific [3H]QNB binding was significantly higher in atria than in ventricles of control rat hearts. The binding to each region was unchanged at 1 and 2 weeks following 6-OHDA treatment, while it was significantly increased in most regions at 3 weeks. There was a 30% increase in the B(max) in right and left atria without a change in the K(d), suggesting a change in the receptor density. The choline acetyltransferase activity was not significantly altered in any region of 60OHDA-treated rat hearts. The present study has demonstrated that destruction of noradrenergic nerve terminals in rats with 6-OHDA leads to an increase in the density of β-adrenergic receptors and a decrease in the NE concentration and that most of the cardiac muscarinic cholinergic receptors are not located on adrenergic neurons.

AB - To characterize the regional changes in β-adrenergic and muscarinic cholinergic receptors in rat hearts following 6-hydroxydopamine (6-OHDA) treatment, receptor binding assys, using the specific ligands [3H]dihydroalprenolol (DHA) β-adrenergic receptor) and [3H]quinuclidinyl benzilate (QNB) (muscarinic cholinergic receptor) were performed in five regions of control and treated hearts. In addition, norepinephrine (NE) concentration and choline acetyltransferase activity in hearts were assayed to characterize the model. Rats were treated with 2 x 50 mg/kg i.v. injections of 6-OHDA.HBr at 24-h intervals and the hearts were removed 1,2, and 3 weeks later. The specific [3H]DHA binding was significantly higher in the ventricles and intraventricular septum than in the right atria of control rat hearts, suggesting a regional variation for β-adrenergic receptors. Following 6-OHDA treatment, the specific [3H]DHA binding to right atria, left ventricles, and ventricular septae significantly increased compared to similar regions of control rat hearts. The B(max) value in left ventricles was significantly increased, by 32, 38, and 17%, respectively, at 1, 2, and 3 weeks without a change in the K(d), suggesting an increase in the density of β-adrenergic receptors. There was a marked (60-80%) reduction of NE levels in all regions of 6-OHDA-treated rat hearts. These results suggest a relationship between the reduction of endogenous NE and the development of the increased density of β-adrenergic receptors in the rat hearts following 6-OHDA treatment. Specific [3H]QNB binding was significantly higher in atria than in ventricles of control rat hearts. The binding to each region was unchanged at 1 and 2 weeks following 6-OHDA treatment, while it was significantly increased in most regions at 3 weeks. There was a 30% increase in the B(max) in right and left atria without a change in the K(d), suggesting a change in the receptor density. The choline acetyltransferase activity was not significantly altered in any region of 60OHDA-treated rat hearts. The present study has demonstrated that destruction of noradrenergic nerve terminals in rats with 6-OHDA leads to an increase in the density of β-adrenergic receptors and a decrease in the NE concentration and that most of the cardiac muscarinic cholinergic receptors are not located on adrenergic neurons.

UR - http://www.scopus.com/inward/record.url?scp=0018961875&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018961875&partnerID=8YFLogxK

M3 - Article

C2 - 6252437

AN - SCOPUS:0018961875

VL - 18

SP - 185

EP - 192

JO - Molecular Pharmacology

JF - Molecular Pharmacology

SN - 0026-895X

IS - 2

ER -