Regulation of β-adrenoceptors by thyroid hormone and amiodarone in rat myocardiac cells in culture

Hyperthyroidism is associated with elevation of heart cells sensitivity to catecholamines. We demonstrated that T₃(10^-8M) increased (30%) the number of β-adrenoceptors in intact heart cells grown in vitro within 48 hr, without changing the affinity of the ligand [³H]CGP-12177. The increase in β-adrenoceptors in T₃-treated myocytes was not associated with an increase in receptor-mediated cAMP production. Amiodarone, an antiarrhythmic drug, reduces the sensitivity of the heart to catecholamines. To investigate this effect, we analysed the influence of amiodarone on the level of β-adrenergic receptors. Ninety minute preincubation with amiodarone (5 × 10^-5 M) decreased the number of β-adrenoceptors (35-50%) in intact heart cells and in heart membranes, without affecting the dissociation constants (K_d). Amiodarone inhibited isoproterenol induced cAMP production. These results indicate that the mechanism of action of amiodarone on the heart seems to be a non-competitive inhibition of catecholamine receptors.