Antagonism between T3 and amiodarone on the contractility and the density of beta-adrenoceptors of chicken cardiac myocytes

Eur J Pharmacol. 1994 Aug 11;261(1-2):97-104. doi: 10.1016/0014-2999(94)90306-9.

Abstract

3,3',5-Triiodothyronine (T3), at 10(-8) M, potentiated by 26.4-30.9% the isoproterenol-mediated inotropic effect in chick embryo cardiac myocytes in culture. Amiodarone (10(-6) M) decreased this response by 44.6% only in cells cultured with serum, where the T3 concentration was 10(-13) M. Amiodarone inhibited the potentiating effect of T3. Amiodarone alone had no influence on the beta-adrenoceptor density in cells cultured in serum-free medium. This confirms that the effects of amiodarone on cardiac beta-adrenoceptors are T3 dependent. T3 increased the density of beta-adrenoceptors through two concentration ranges, with an initial 30% increase between 10(-14) and 10(-11) M, followed by a second increase until 10(-7) M. Amiodarone not only inhibited the first positive effect of T3 but also decreased beta-adrenoceptor density far below the control value. The second positive T3 effect was also inhibited by 50% by amiodarone. This study suggests that T3 might increase the number of cell-surface beta-adrenoceptors and modify their cellular traffic through at least two mechanisms, one assumed to be non-genomic, the other being genomic, and that amiodarone could affect the two mechanisms differently.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Amiodarone / antagonists & inhibitors
  • Amiodarone / pharmacology*
  • Animals
  • Calcium / pharmacology
  • Chick Embryo
  • Heart / drug effects
  • Iodocyanopindolol
  • Isoproterenol / pharmacology
  • Myocardial Contraction / drug effects*
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Myocardium / ultrastructure
  • Pindolol / analogs & derivatives
  • Pindolol / pharmacology
  • Propanolamines / pharmacology
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / metabolism*
  • Triiodothyronine / antagonists & inhibitors
  • Triiodothyronine / pharmacology*

Substances

  • Adrenergic beta-Antagonists
  • Propanolamines
  • Receptors, Adrenergic, beta
  • Triiodothyronine
  • Iodocyanopindolol
  • Pindolol
  • Isoproterenol
  • Amiodarone
  • CGP 12177
  • Calcium