Specific high affinity binding of the calcium channel antagonist, [3H]nitrendipine, to rat liver microsomes

V. Gopalakrishnan, Christopher Triggle

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Some key properties of the binding of [3H]nitrendipine, an analogue of the 1,4-dihydropyridine, nifedipine, to a plasma membrane enriched microsomal fraction from the rat liver are described. Specific binding was saturable, linear with protein concentration, and reversible. The apparent equilibrium dissociation constant, K(D), was 4.20 ± 0.22 nM and the maximum density of binding, B(max), was 3.02 ± 0.17 pmol/mg of protein determined from Scatchard analysis of binding at 10°C. Inhibition of binding was specific for dihydropyridines with competitive inhibition being noted with nifedipine and 4-chloronifedipine, as well as BAY K-8644, a calcium channel agonist. A biphasic displacement curve was recorded for methoxy verapamil (D-600), and a triphasic competition curve with lanthanum (La3+), and diltiazem demonstrated competitive kinetics. The high affinity binding site for nitrendipine in the liver, although having some similar properties to those sites described in skeletal muscle, would appear to be distinctive with respect to its unique sensitivity to D-600 and diltiazem. We speculate that this binding site may represent a Ca2+ channel responsible for regulating Ca2+ influx and hepatic glycogenolysis.

Original languageEnglish
Pages (from-to)1249-1252
Number of pages4
JournalCanadian Journal of Physiology and Pharmacology
Volume62
Issue number9
Publication statusPublished - 1984
Externally publishedYes

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Nitrendipine
Calcium Channel Blockers
Liver Microsomes
Gallopamil
Diltiazem
Nifedipine
Liver
Calcium Channel Agonists
Binding Sites
Dihydropyridines
Glycogenolysis
Lanthanum
Verapamil
Skeletal Muscle
Proteins
Cell Membrane

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology
  • Pharmacology
  • Physiology (medical)

Cite this

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abstract = "Some key properties of the binding of [3H]nitrendipine, an analogue of the 1,4-dihydropyridine, nifedipine, to a plasma membrane enriched microsomal fraction from the rat liver are described. Specific binding was saturable, linear with protein concentration, and reversible. The apparent equilibrium dissociation constant, K(D), was 4.20 ± 0.22 nM and the maximum density of binding, B(max), was 3.02 ± 0.17 pmol/mg of protein determined from Scatchard analysis of binding at 10°C. Inhibition of binding was specific for dihydropyridines with competitive inhibition being noted with nifedipine and 4-chloronifedipine, as well as BAY K-8644, a calcium channel agonist. A biphasic displacement curve was recorded for methoxy verapamil (D-600), and a triphasic competition curve with lanthanum (La3+), and diltiazem demonstrated competitive kinetics. The high affinity binding site for nitrendipine in the liver, although having some similar properties to those sites described in skeletal muscle, would appear to be distinctive with respect to its unique sensitivity to D-600 and diltiazem. We speculate that this binding site may represent a Ca2+ channel responsible for regulating Ca2+ influx and hepatic glycogenolysis.",
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AU - Gopalakrishnan, V.

AU - Triggle, Christopher

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N2 - Some key properties of the binding of [3H]nitrendipine, an analogue of the 1,4-dihydropyridine, nifedipine, to a plasma membrane enriched microsomal fraction from the rat liver are described. Specific binding was saturable, linear with protein concentration, and reversible. The apparent equilibrium dissociation constant, K(D), was 4.20 ± 0.22 nM and the maximum density of binding, B(max), was 3.02 ± 0.17 pmol/mg of protein determined from Scatchard analysis of binding at 10°C. Inhibition of binding was specific for dihydropyridines with competitive inhibition being noted with nifedipine and 4-chloronifedipine, as well as BAY K-8644, a calcium channel agonist. A biphasic displacement curve was recorded for methoxy verapamil (D-600), and a triphasic competition curve with lanthanum (La3+), and diltiazem demonstrated competitive kinetics. The high affinity binding site for nitrendipine in the liver, although having some similar properties to those sites described in skeletal muscle, would appear to be distinctive with respect to its unique sensitivity to D-600 and diltiazem. We speculate that this binding site may represent a Ca2+ channel responsible for regulating Ca2+ influx and hepatic glycogenolysis.

AB - Some key properties of the binding of [3H]nitrendipine, an analogue of the 1,4-dihydropyridine, nifedipine, to a plasma membrane enriched microsomal fraction from the rat liver are described. Specific binding was saturable, linear with protein concentration, and reversible. The apparent equilibrium dissociation constant, K(D), was 4.20 ± 0.22 nM and the maximum density of binding, B(max), was 3.02 ± 0.17 pmol/mg of protein determined from Scatchard analysis of binding at 10°C. Inhibition of binding was specific for dihydropyridines with competitive inhibition being noted with nifedipine and 4-chloronifedipine, as well as BAY K-8644, a calcium channel agonist. A biphasic displacement curve was recorded for methoxy verapamil (D-600), and a triphasic competition curve with lanthanum (La3+), and diltiazem demonstrated competitive kinetics. The high affinity binding site for nitrendipine in the liver, although having some similar properties to those sites described in skeletal muscle, would appear to be distinctive with respect to its unique sensitivity to D-600 and diltiazem. We speculate that this binding site may represent a Ca2+ channel responsible for regulating Ca2+ influx and hepatic glycogenolysis.

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