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

Overview

MeSH Major

  • Calcium Channel Blockers
  • Microsomes, Liver
  • Nifedipine

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, KD, was 4.20 +/- 0.22 nM and the maximum density of binding, Bmax, was 3.02 +/- 0.17 pmol/mg of protein determined from Scatchard analysis of binding at 10 degrees 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.

publication date

  • January 1984

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 6498637

Additional Document Info

start page

  • 1249

end page

  • 52

volume

  • 62

number

  • 9