Amiodarone has exclusively non-genomic action on cardiac beta-adrenoceptorregulation

The antiarrhythmic drug amiodarone down-regulates the density of cardiac be ta -adrenoceptors behaving as a triiodothyronine (T-3) antagonist. It is st ill unclear if amiodarone acts at the nuclear (genomic) and/or the non-geno mic levels. Using Northern blot analysis, we showed that the amiodarone had no effect on the increase of beta (1)-adrenoceptor mRNA level induced by t he T-3-administration in the heart of thyroidectomised rats. Thus, our resu lts suggest that amiodarone has no genomic effect. Consequently, we investi gated whether amiodarone down-regulation of beta -adrenoceptor number in T- 3-stimulated cardiomyocytes could be explained by changes in the rate of ce ll surface receptor protein turnover. Indeed, the binding studies of cycloh exidemide-treated cells showed that amiodarone suppressed the T-3-induced d ecrease in the rate of the cell surface receptor disappearance. In conclusi on, our findings indicate that the modulation of cardiac beta -adrenoceptor density by amiodarone involves only non-genomic targets required in T-3-de pendent regulation of the cell surface beta -adrenoceptor turnover. (C) 200 0 Elsevier Science B.V. All rights reserved.