Amiodarone has exclusively non-genomic action on cardiac beta-adrenoceptor regulation.
The antiarrhythmic drug amiodarone down-regulates the density of cardiac beta-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 beta(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 beta-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 beta-adrenoceptor density by amiodarone involves only non-genomic targets required in T(3)-dependent regulation of the cell surface beta-adrenoceptor turnover.
Vassy
R
R
Laboratoire de Pharmacologie Clinique et Experimentale, EA 2360, Faculté de Médecine, Université Paris-Nord, 74, rue Marcel Cachin, 93017 Cedex, Bobigny, France.
Starzec
A
A
Yin
Y
Y
Nicolas
P
P
Perret
G Y
GY
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D006321:Heart / Q000254:growth & development; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D012313:RNA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D011956:Receptors, Cell Surface; D014284:Triiodothyronine; D012313:RNA; D000638:Amiodarone