ANTAGONISM BETWEEN T-3 AND AMIODARONE ON THE CONTRACTILITY AND THE DENSITY OF BETA-ADRENOCEPTORS OF CHICKEN CARDIAC MYOCYTES

3,3',5-Triiodothyronine (T-3), at 10(-8) M, potentiated by 26.4-30.9% the isoproterenol-mediated inotropic effect in chick embryo cardiac my ocytes in culture. Amiodarone (10(-6) M) decreased this response by 44 .6% only in cells cultured with serum, where the T-3 concentration was 10(-13) M. Amiodarone inhibited the potentiating effect of T-3. Amiod arone alone had no influence on the beta-adrenoceptor density in cells cultured in serum-free medium. This confirms that the effects of amio darone on cardiac beta-adrenoceptors are T-3 dependent. T-3 increased the density of beta-adrenoceptors through two concentration ranges, wi th 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 f irst positive effect of T-3 but also decreased beta-adrenoceptor densi ty far below the control value. The second positive T-3 effect was als o inhibited by 50% by amiodarone. This study suggests that T-3 might i ncrease the number of cell-surface beta-adrenoceptors and modify their cellular traffic through at least two mechanisms, one assumed to be n on-genomic, the other being genomic, and that amiodarone could affect the two mechanisms differently.