Elsevier

Biochemical Pharmacology

Volume 32, Issue 17, 1 September 1983, Pages 2473-2477
Biochemical Pharmacology

Cardiac β-adrenoceptor modulation by amiodarone

https://doi.org/10.1016/0006-2952(83)90004-7Get rights and content

Abstract

β-Antiadrenergic properties are part of the pharmacological characteristics of amiodarone. In the present study, the action of amiodarone on rat-heart β-adrenoceptors was investigated. [125I]Cyanopindolol (CYP) was used to label β-adrenoceptors in crude rat-heart microsomes. In competition binding experiments, amiodarone up to 10−6 M did not displace [125I]CYP from cardiac β-adrenergic receptors. The effects of amiodarone on the number and affinity for [125I]CYP of β-adrenoceptors were evaluated in saturation experiments. In vitro exposure of cardiac microsomes to 10−5 M amiodarone did not modify these parameters. At higher concentrations the β-receptor number decreased while the affinity for [125I]CYP was not affected. In vivo experiments showed a significant decrease in β-adrenoceptor density after a single oral dose of 50 mg/kg amiodarone. In chronically treated animals, the same decrease in β-receptor number was observed 24 hr after the last administration of the drug. 5′-Nucleotidase activity, another specific marker of the plasma membrane, was unaffected by the treatment. These results suggest that part of the β-adrenergic antagonism of amiodarone is due to a decrease in the β-adrenoceptor density at the surface of the myocardial cell.

References (23)

  • F.I. Marcus et al.

    Am. Heart J.

    (1981)
  • P. Polster et al.

    Biochem. Pharmac.

    (1976)
  • O.H. Lowry et al.

    J. biol. Chem.

    (1951)
  • C.H. Fiske et al.

    J. biol. Chem.

    (1925)
  • O.E. Brodde

    Biochem. Pharmac.

    (1982)
  • P. Robberecht et al.

    Biochem. Pharmac.

    (1981)
  • R. Charlier et al.

    Arzneimittel-Forsch.

    (1968)
  • R. Charlier

    B. J. Pharmac.

    (1970)
  • G. Engel et al.

    Naunyn-Schmiedeberg's Archs Pharmac.

    (1981)
  • D. Hoyer et al.

    Naunyn-Schmiedeberg's Archs Pharmac.

    (1982)
  • Y. Berger, J. E. Matteazzi, M. Pacco, G. Houin, J. P. Tillement and W. Cautreels, in...
  • Cited by (64)

    • Concentration dependent mitochondrial effect of amiodarone

      2003, Biochemical Pharmacology
      Citation Excerpt :

      Amiodarone (2-butyl-3-benzofuranyl-4-[2-(diethylamino)-ethoxy]-3,5-diiodophenyl-ketone hydrochloride), a class III antiarrhythmic agent prolongs action potential duration which effect may involve blocking of β-adrenergic receptors, sodium channels and L-type calcium channels [1–4].

    View all citing articles on Scopus
    View full text