Amiodarone has exclusively non-genomic action on cardiac β-adrenoceptor regulation

Abstract

The antiarrhythmic drug amiodarone down-regulates the density of cardiac β-adrenoceptors behaving as a triiodothyronine (T 3) antagonist. It is still unclear if amiodarone acts at the nuclear (genomic) and/or the non-genomic levels. Using Northern blot analysis, we showed that the amiodarone had no effect on the increase of β 1-adrenoceptor mRNA level induced by the T 3-administration in the heart of thyroidectomised rats. Thus, our results suggest that amiodarone has no genomic effect. Consequently, we investigated whether amiodarone down-regulation of β-adrenoceptor number in T 3-stimulated cardiomyocytes could be explained by changes in the rate of cell surface receptor protein turnover. Indeed, the binding studies of cyclohexidemide-treated cells showed that amiodarone suppressed the T 3-induced decrease in the rate of the cell surface receptor disappearance. In conclusion, our findings indicate that the modulation of cardiac β-adrenoceptor density by amiodarone involves only non-genomic targets required in T 3-dependent regulation of the cell surface β-adrenoceptor turnover.