Measurement of functional cholinergic innervation in rat heart with a novel vesamicol receptor ligand

Paul R. Coffeen; S. M.N. Efange; George C. Haidet; Scott McKnite; Rosemary B. Langason; A. B. Khare; Jennifer Pennington; Keith G. Lurie

doi:10.1016/S0969-8051(96)00132-1

Measurement of functional cholinergic innervation in rat heart with a novel vesamicol receptor ligand

Paul R. Coffeen, S. M.N. Efange, George C. Haidet, Scott McKnite, Rosemary B. Langason, A. B. Khare, Jennifer Pennington, Keith G. Lurie

Medicine - Cardiology Division

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

7 Scopus citations

Abstract

Regional differences in cholinergic activity in the cardiac conduction system have been difficult to study, We tested the utility of (+)-m-[¹²⁵I]iodobenzyl)trozamicol(+)-[¹²⁵I]MIBT, a novel radio ligand that binds to the vesamicol receptor located on the synaptic vesicle in presynaptic cholinergic neurons, as a functional marker of cholinergic activity in the conduction system. The (+)-[¹²⁵I]MIBT was injected intravenously into four rats. Three hours later, the rats were killed and their hearts were frozen. Quantitative autoradiography was performed on 20-micron-thick sections that were subsequently stained for acetylcholinesterase to identify specific conduction system elements. Marked similarities existed between (+)-[¹²⁵I]MIBT uptake and acetylcholinesterase positive regions. Optical densitometric analysis of regional (+)-[¹²⁵I]MIBT uptake revealed significantly greater (+)-[¹²⁵I]MIBT binding (nCi/mg) in the atrioventricular node (AVN) and His bundle regions compared with other conduction and contractile elements (AVN: 3.43 ± 0.37; His bundle: 2.16 ± 0.30; right bundle branch: 0.95 ± 0.13; right atrium: 0.68 ± 0.05; right ventricle: 0.57 ± 0.03; and left ventricle: 0.57 ± 0.03; p < 0.05 comparing conduction elements with ventricular muscle). This study demonstrates that (+)-[¹²⁵I]MIBT binds avidly to cholinergic nerve tissue innervating specific conduction system elements, Thus, (+)-[¹²⁵I]MIBT may be a useful functional marker in studies on cholinergic innervation in the cardiac conduction system.

Original language	English (US)
Pages (from-to)	923-926
Number of pages	4
Journal	Nuclear Medicine and Biology
Volume	23
Issue number	7
DOIs	https://doi.org/10.1016/S0969-8051(96)00132-1
State	Published - Oct 1996

Bibliographical note

Funding Information:
This work was supportedb y theA mericanH eart Association,M innesota Affiliate, Grant-in Aid. Part of thisw ork was presented in abstract fom at theN orth American Society of Pacinga nd Elecnophysiologmy eeting, May 1993. The authorst hankB arry Detlofff or his technicaal ssistance.

Keywords

Acetylcholine
Autonomic nervous system
Cardiac conduction system
Receptor autoradiography
Vesamicol

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10.1016/S0969-8051(96)00132-1

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title = "Measurement of functional cholinergic innervation in rat heart with a novel vesamicol receptor ligand",

abstract = "Regional differences in cholinergic activity in the cardiac conduction system have been difficult to study, We tested the utility of (+)-m-[125I]iodobenzyl)trozamicol(+)-[125I]MIBT, a novel radio ligand that binds to the vesamicol receptor located on the synaptic vesicle in presynaptic cholinergic neurons, as a functional marker of cholinergic activity in the conduction system. The (+)-[125I]MIBT was injected intravenously into four rats. Three hours later, the rats were killed and their hearts were frozen. Quantitative autoradiography was performed on 20-micron-thick sections that were subsequently stained for acetylcholinesterase to identify specific conduction system elements. Marked similarities existed between (+)-[125I]MIBT uptake and acetylcholinesterase positive regions. Optical densitometric analysis of regional (+)-[125I]MIBT uptake revealed significantly greater (+)-[125I]MIBT binding (nCi/mg) in the atrioventricular node (AVN) and His bundle regions compared with other conduction and contractile elements (AVN: 3.43 ± 0.37; His bundle: 2.16 ± 0.30; right bundle branch: 0.95 ± 0.13; right atrium: 0.68 ± 0.05; right ventricle: 0.57 ± 0.03; and left ventricle: 0.57 ± 0.03; p < 0.05 comparing conduction elements with ventricular muscle). This study demonstrates that (+)-[125I]MIBT binds avidly to cholinergic nerve tissue innervating specific conduction system elements, Thus, (+)-[125I]MIBT may be a useful functional marker in studies on cholinergic innervation in the cardiac conduction system.",

keywords = "Acetylcholine, Autonomic nervous system, Cardiac conduction system, Receptor autoradiography, Vesamicol",

author = "Coffeen, {Paul R.} and Efange, {S. M.N.} and Haidet, {George C.} and Scott McKnite and Langason, {Rosemary B.} and Khare, {A. B.} and Jennifer Pennington and Lurie, {Keith G.}",

note = "Funding Information: This work was supportedb y theA mericanH eart Association,M innesota Affiliate, Grant-in Aid. Part of thisw ork was presented in abstract fom at theN orth American Society of Pacinga nd Elecnophysiologmy eeting, May 1993. The authorst hankB arry Detlofff or his technicaal ssistance.",

year = "1996",

month = oct,

doi = "10.1016/S0969-8051(96)00132-1",

language = "English (US)",

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T1 - Measurement of functional cholinergic innervation in rat heart with a novel vesamicol receptor ligand

AU - Coffeen, Paul R.

AU - Efange, S. M.N.

AU - Haidet, George C.

AU - McKnite, Scott

AU - Langason, Rosemary B.

AU - Khare, A. B.

AU - Pennington, Jennifer

AU - Lurie, Keith G.

N1 - Funding Information: This work was supportedb y theA mericanH eart Association,M innesota Affiliate, Grant-in Aid. Part of thisw ork was presented in abstract fom at theN orth American Society of Pacinga nd Elecnophysiologmy eeting, May 1993. The authorst hankB arry Detlofff or his technicaal ssistance.

PY - 1996/10

Y1 - 1996/10

N2 - Regional differences in cholinergic activity in the cardiac conduction system have been difficult to study, We tested the utility of (+)-m-[125I]iodobenzyl)trozamicol(+)-[125I]MIBT, a novel radio ligand that binds to the vesamicol receptor located on the synaptic vesicle in presynaptic cholinergic neurons, as a functional marker of cholinergic activity in the conduction system. The (+)-[125I]MIBT was injected intravenously into four rats. Three hours later, the rats were killed and their hearts were frozen. Quantitative autoradiography was performed on 20-micron-thick sections that were subsequently stained for acetylcholinesterase to identify specific conduction system elements. Marked similarities existed between (+)-[125I]MIBT uptake and acetylcholinesterase positive regions. Optical densitometric analysis of regional (+)-[125I]MIBT uptake revealed significantly greater (+)-[125I]MIBT binding (nCi/mg) in the atrioventricular node (AVN) and His bundle regions compared with other conduction and contractile elements (AVN: 3.43 ± 0.37; His bundle: 2.16 ± 0.30; right bundle branch: 0.95 ± 0.13; right atrium: 0.68 ± 0.05; right ventricle: 0.57 ± 0.03; and left ventricle: 0.57 ± 0.03; p < 0.05 comparing conduction elements with ventricular muscle). This study demonstrates that (+)-[125I]MIBT binds avidly to cholinergic nerve tissue innervating specific conduction system elements, Thus, (+)-[125I]MIBT may be a useful functional marker in studies on cholinergic innervation in the cardiac conduction system.

AB - Regional differences in cholinergic activity in the cardiac conduction system have been difficult to study, We tested the utility of (+)-m-[125I]iodobenzyl)trozamicol(+)-[125I]MIBT, a novel radio ligand that binds to the vesamicol receptor located on the synaptic vesicle in presynaptic cholinergic neurons, as a functional marker of cholinergic activity in the conduction system. The (+)-[125I]MIBT was injected intravenously into four rats. Three hours later, the rats were killed and their hearts were frozen. Quantitative autoradiography was performed on 20-micron-thick sections that were subsequently stained for acetylcholinesterase to identify specific conduction system elements. Marked similarities existed between (+)-[125I]MIBT uptake and acetylcholinesterase positive regions. Optical densitometric analysis of regional (+)-[125I]MIBT uptake revealed significantly greater (+)-[125I]MIBT binding (nCi/mg) in the atrioventricular node (AVN) and His bundle regions compared with other conduction and contractile elements (AVN: 3.43 ± 0.37; His bundle: 2.16 ± 0.30; right bundle branch: 0.95 ± 0.13; right atrium: 0.68 ± 0.05; right ventricle: 0.57 ± 0.03; and left ventricle: 0.57 ± 0.03; p < 0.05 comparing conduction elements with ventricular muscle). This study demonstrates that (+)-[125I]MIBT binds avidly to cholinergic nerve tissue innervating specific conduction system elements, Thus, (+)-[125I]MIBT may be a useful functional marker in studies on cholinergic innervation in the cardiac conduction system.

KW - Acetylcholine

KW - Autonomic nervous system

KW - Cardiac conduction system

KW - Receptor autoradiography

KW - Vesamicol

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Measurement of functional cholinergic innervation in rat heart with a novel vesamicol receptor ligand

Abstract

Bibliographical note

Keywords

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