Diltiazem enhancement of [3H]nitrendipine binding to calcium channel associated drug receptor sites in rat brain synaptosomes

Henry I. Yamamura; Hans Schoemaker; Richard G. Boles; William R. Roeske

doi:10.1016/0006-291X(82)90877-4

Diltiazem enhancement of [³H]nitrendipine binding to calcium channel associated drug receptor sites in rat brain synaptosomes

Henry I. Yamamura, Hans Schoemaker, Richard G. Boles, William R. Roeske

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

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Abstract

The binding of the dihydropyridine calcium channel antagonist [³H]nitrendipine to whole rat brain synaptosomes was studied. Binding was specific, saturable, and of high affinity (K_d = 170 pM). The calcium channel antagonist diltiazem enhanced [³H]nitrendipine binding in synaptosomes in concentrations of 1 and 10 μM. Equilibrium saturation analysis demonstrated that this effect was mediated by a decrease in the dissociation constant, due to a 3-fold reduction in the rate of ligand-receptor complex dissociation. It is concluded that diltiazem allosterically modulates the calcium channel drug receptor labeled by [³H]nitrendipine in this preparation.

Original language	English (US)
Pages (from-to)	640-646
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	108
Issue number	2
DOIs	https://doi.org/10.1016/0006-291X(82)90877-4
State	Published - Sep 30 1982

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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@article{f4a3527e358c46bb84bc3e448a774a06,

title = "Diltiazem enhancement of [3H]nitrendipine binding to calcium channel associated drug receptor sites in rat brain synaptosomes",

abstract = "The binding of the dihydropyridine calcium channel antagonist [3H]nitrendipine to whole rat brain synaptosomes was studied. Binding was specific, saturable, and of high affinity (Kd = 170 pM). The calcium channel antagonist diltiazem enhanced [3H]nitrendipine binding in synaptosomes in concentrations of 1 and 10 μM. Equilibrium saturation analysis demonstrated that this effect was mediated by a decrease in the dissociation constant, due to a 3-fold reduction in the rate of ligand-receptor complex dissociation. It is concluded that diltiazem allosterically modulates the calcium channel drug receptor labeled by [3H]nitrendipine in this preparation.",

author = "Yamamura, {Henry I.} and Hans Schoemaker and Boles, {Richard G.} and Roeske, {William R.}",

note = "Funding Information: The authors thank Alice Barrett for secretarial assistance and Tom Toneff for technical assistance. This study was supported in part by USPES grants ME-30626, YE-27251, and a Program Project Grant EL-20984, a Research Scientist Development Award Type II (ME-00095) from the National Institute of Mental Health to H.I.Y.. and a Research Scientist Development Award (HL-00776) from the National Heart. Lung, and Blood Institute to W.R.R.",

year = "1982",

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doi = "10.1016/0006-291X(82)90877-4",

language = "English (US)",

volume = "108",

pages = "640--646",

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T1 - Diltiazem enhancement of [3H]nitrendipine binding to calcium channel associated drug receptor sites in rat brain synaptosomes

AU - Yamamura, Henry I.

AU - Schoemaker, Hans

AU - Boles, Richard G.

AU - Roeske, William R.

N1 - Funding Information: The authors thank Alice Barrett for secretarial assistance and Tom Toneff for technical assistance. This study was supported in part by USPES grants ME-30626, YE-27251, and a Program Project Grant EL-20984, a Research Scientist Development Award Type II (ME-00095) from the National Institute of Mental Health to H.I.Y.. and a Research Scientist Development Award (HL-00776) from the National Heart. Lung, and Blood Institute to W.R.R.

PY - 1982/9/30

Y1 - 1982/9/30

N2 - The binding of the dihydropyridine calcium channel antagonist [3H]nitrendipine to whole rat brain synaptosomes was studied. Binding was specific, saturable, and of high affinity (Kd = 170 pM). The calcium channel antagonist diltiazem enhanced [3H]nitrendipine binding in synaptosomes in concentrations of 1 and 10 μM. Equilibrium saturation analysis demonstrated that this effect was mediated by a decrease in the dissociation constant, due to a 3-fold reduction in the rate of ligand-receptor complex dissociation. It is concluded that diltiazem allosterically modulates the calcium channel drug receptor labeled by [3H]nitrendipine in this preparation.

AB - The binding of the dihydropyridine calcium channel antagonist [3H]nitrendipine to whole rat brain synaptosomes was studied. Binding was specific, saturable, and of high affinity (Kd = 170 pM). The calcium channel antagonist diltiazem enhanced [3H]nitrendipine binding in synaptosomes in concentrations of 1 and 10 μM. Equilibrium saturation analysis demonstrated that this effect was mediated by a decrease in the dissociation constant, due to a 3-fold reduction in the rate of ligand-receptor complex dissociation. It is concluded that diltiazem allosterically modulates the calcium channel drug receptor labeled by [3H]nitrendipine in this preparation.

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U2 - 10.1016/0006-291X(82)90877-4

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AN - SCOPUS:0020334268

SN - 0006-291X

VL - 108

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EP - 646

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -

Diltiazem enhancement of [³H]nitrendipine binding to calcium channel associated drug receptor sites in rat brain synaptosomes

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