Sodium-dependent high-affinity binding of [3H] hemicholinium-3 in the rat brain: A potentially selective marker for presynaptic cholinergic sites

Thomas W. Vickroy; William R. Roeske; Henry I. Yamamura

doi:10.1016/0024-3205(84)90525-3

Sodium-dependent high-affinity binding of [³H] hemicholinium-3 in the rat brain: A potentially selective marker for presynaptic cholinergic sites

Thomas W. Vickroy, William R. Roeske, Henry I. Yamamura

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Abstract

This report describes the membrane binding properties of [³H] hemicholinium-3 ([³H]HC-3), a selective inhibitor of sodium-dependent high-affinity choline uptake (SDHACU) in cholinergic nerve terminals. Under the described assay conditions, [³H]HC-3 binds with a saturable population of high-affinity (apparent K_d=1.9 nM) CNS membrane sites having the regional distribution: striatum ≫ hippocampus > cerebral cortex > cerebellum. High-affinity [³H]HC-3 binding is entirely dependent upon the presence of sodium chloride (EC₅₀=35-50 mM) and is markedly reduced when other salts of sodium or monovalent ions are substituted. [³H]HC-3 binding is inhibited by choline (K_i=6μM) and acetylcholine (K_i=35μM) but markedly less sensitive to other cholinergic agents and metabolic inhibitors. In light of the similar ionic dependencies, regional distributions and pharmacological specificities of [³H]HC-3 binding and SDHACU, closely associated sites may be involved in both processes.

Original language	English (US)
Pages (from-to)	2335-2343
Number of pages	9
Journal	Life Sciences
Volume	35
Issue number	23
DOIs	https://doi.org/10.1016/0024-3205(84)90525-3
State	Published - Dec 3 1984

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
Pharmacology, Toxicology and Pharmaceutics(all)

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10.1016/0024-3205(84)90525-3

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title = "Sodium-dependent high-affinity binding of [3H] hemicholinium-3 in the rat brain: A potentially selective marker for presynaptic cholinergic sites",

abstract = "This report describes the membrane binding properties of [3H] hemicholinium-3 ([3H]HC-3), a selective inhibitor of sodium-dependent high-affinity choline uptake (SDHACU) in cholinergic nerve terminals. Under the described assay conditions, [3H]HC-3 binds with a saturable population of high-affinity (apparent Kd=1.9 nM) CNS membrane sites having the regional distribution: striatum ≫ hippocampus > cerebral cortex > cerebellum. High-affinity [3H]HC-3 binding is entirely dependent upon the presence of sodium chloride (EC50=35-50 mM) and is markedly reduced when other salts of sodium or monovalent ions are substituted. [3H]HC-3 binding is inhibited by choline (Ki=6μM) and acetylcholine (Ki=35μM) but markedly less sensitive to other cholinergic agents and metabolic inhibitors. In light of the similar ionic dependencies, regional distributions and pharmacological specificities of [3H]HC-3 binding and SDHACU, closely associated sites may be involved in both processes.",

author = "Vickroy, {Thomas W.} and Roeske, {William R.} and Yamamura, {Henry I.}",

note = "Funding Information: The authors wish to acknowledget he excellent technical assistance of Martha Ackermana nd secretarial assistance of Pat Gonzalez. This work was supported in part by grants from the American Heart Association Arizona Affiliate and USPHS grants MH-27257a nd MH-30636. T.W.V. is supported by a National Research Service Award from The National Heart, Lung and Blood Institute. W.R.R. and H.I.Y. are supported by a Type II RSDA (MH-O0095)a nd a RCDA (HL-00776), respectively.",

year = "1984",

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doi = "10.1016/0024-3205(84)90525-3",

language = "English (US)",

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T1 - Sodium-dependent high-affinity binding of [3H] hemicholinium-3 in the rat brain

T2 - A potentially selective marker for presynaptic cholinergic sites

AU - Vickroy, Thomas W.

AU - Roeske, William R.

AU - Yamamura, Henry I.

N1 - Funding Information: The authors wish to acknowledget he excellent technical assistance of Martha Ackermana nd secretarial assistance of Pat Gonzalez. This work was supported in part by grants from the American Heart Association Arizona Affiliate and USPHS grants MH-27257a nd MH-30636. T.W.V. is supported by a National Research Service Award from The National Heart, Lung and Blood Institute. W.R.R. and H.I.Y. are supported by a Type II RSDA (MH-O0095)a nd a RCDA (HL-00776), respectively.

PY - 1984/12/3

Y1 - 1984/12/3

N2 - This report describes the membrane binding properties of [3H] hemicholinium-3 ([3H]HC-3), a selective inhibitor of sodium-dependent high-affinity choline uptake (SDHACU) in cholinergic nerve terminals. Under the described assay conditions, [3H]HC-3 binds with a saturable population of high-affinity (apparent Kd=1.9 nM) CNS membrane sites having the regional distribution: striatum ≫ hippocampus > cerebral cortex > cerebellum. High-affinity [3H]HC-3 binding is entirely dependent upon the presence of sodium chloride (EC50=35-50 mM) and is markedly reduced when other salts of sodium or monovalent ions are substituted. [3H]HC-3 binding is inhibited by choline (Ki=6μM) and acetylcholine (Ki=35μM) but markedly less sensitive to other cholinergic agents and metabolic inhibitors. In light of the similar ionic dependencies, regional distributions and pharmacological specificities of [3H]HC-3 binding and SDHACU, closely associated sites may be involved in both processes.

AB - This report describes the membrane binding properties of [3H] hemicholinium-3 ([3H]HC-3), a selective inhibitor of sodium-dependent high-affinity choline uptake (SDHACU) in cholinergic nerve terminals. Under the described assay conditions, [3H]HC-3 binds with a saturable population of high-affinity (apparent Kd=1.9 nM) CNS membrane sites having the regional distribution: striatum ≫ hippocampus > cerebral cortex > cerebellum. High-affinity [3H]HC-3 binding is entirely dependent upon the presence of sodium chloride (EC50=35-50 mM) and is markedly reduced when other salts of sodium or monovalent ions are substituted. [3H]HC-3 binding is inhibited by choline (Ki=6μM) and acetylcholine (Ki=35μM) but markedly less sensitive to other cholinergic agents and metabolic inhibitors. In light of the similar ionic dependencies, regional distributions and pharmacological specificities of [3H]HC-3 binding and SDHACU, closely associated sites may be involved in both processes.

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Sodium-dependent high-affinity binding of [³H] hemicholinium-3 in the rat brain: A potentially selective marker for presynaptic cholinergic sites

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