Desethylamiodarone is a competitive inhibitor of the binding of thyroid hormone to the thyroid hormone α1-receptor protein

• Published in: Molecular and cellular endocrinology 1995, Vol.112 (1), p.15-19
• Main Authors: van Beeren, H.C., Bakker, O., Wiersinga, W.M.
• Format: Article
• Language: English
• Subjects: Desethylamiodarone (DEA); Triiodothyronine (T 3); α1-Thyroid hormone receptor (T 3R)
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/0303-7207(95)03578-U

Desethylamiodarone (DEA), the major metabolite of the potent antiarrythmic drug amiodarone, is a non-competitive inhibitor of the binding of thyroid hormone (T 3) to the β1-thyroid hormone receptor (T 3R). In the present study, we investigated whether DEA acts in a similar way with respect to the α1-T 3R. The chicken α1-T 3R, expressed in an E. coli system, was incubated in the presence or absence of DEA with [ 125I]T 3 in buffer containing 0.05% Triton X-100, 0.05% BSA and 1% ethanol (v/v) in order to solubilise DEA. DEA, but not amiodarone, inhibited T 3 binding in a dose-dependent manner; the IC 50 value was 3.5 × 10 −5 M. Scatchard analyses in the presence of DEA demonstrated a dose-dependent decrease in K a values, but no change in MBC. Lineweaver-Burk plots clearly indicated competitive inhibition by DEA. Pre-incubation of the α1-receptor with DEA decreased maximal [ 125I]T 3 binding, which was independent of the duration of pre-incubation. In conclusion, in contrast to the β1-T 3R, where DEA acts as a non-competitive inhibitor, we now report as a new finding the competitive action of DEA to the α1-T 3R.