Interaction of amiodarone and triiodothyronine on the expression of beta-adrenoceptors in brown adipose tissue of rat

1 This study was undertaken to evaluate in vivo the influence of amiodarone on the effects of triiodothyronine (T3) in brown adipose tissue (BAT) whic h are independent of thyroid hormone synthesis and of the conversion of thy roxine (T4) to T3. Thyroidectomized rats were given a replacement dose of T 3 (0.5 mg kg(-1) p.o. daily for 3 days) with or without amiodarone (50 mg k g(-1) p.o. daily for 1 week). 2 As assessed by RT - PCR, treatment of thyroidectomized rats with T3 cause d a 2 fold decrease in beta 3-adrenoceptor (beta 3-AR) mRNA levels and a 2 fold increase in beta 1-AR mRNA levels. 3 Binding studies using [H-3]-CGP 12177 as a ligand showed that treatment o f thyoidectomized rats with T3 resulted in a 70% decrease in beta 3-AR numb er and in an 80% increase in beta 1-AR in BAT membranes. 4 T3-treatment abolished the increase in BAT adenylyl cyclase (AC) activity induced by CGP12177 in thyroidectomized rats. It also decreased the amount of G(i) protein (ADP-ribosylation) by 30%. 5 At variance with the literature on the heart, amiodarone administration d id not inhibit the positive effect of T3 on beta 1-AR expression in BAT in thyroidectomized rats. However, it antagonized the effect of T3 on beta 3-A R number, but not on AC activity or on G(i) expression. 6 These results indicate that the effects of thyroid hormones on the respon siveness of BAT to catecholamines involves both receptor and post-receptor mechanisms, they also suggest that interaction between amiodarone and thyro id hormones is highly tissue-specific and depends on the beta-AR subtype.