Interaction of amiodarone and triiodothyronine on the expression of β-adrenoceptors in brown adipose tissue of rat
Interaction of amiodarone and triiodothyronine on the expression of β-adrenoceptors in brown adipose tissue of rat
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DOI：
10.1038/sj.bjp.0702456
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发表时间：
1999-03-01
影响因子：
7.3
通讯作者：
Perret, GY
中科院分区：
文献类型：
--
作者：
Adli, H;Bazin, R;Perret, GY
1本研究旨在评价胺碘酮对棕色脂肪组织（BAT）中三碘甲状腺原氨酸（T3）效应的体内影响，该效应与甲状腺激素合成和甲状腺素（T4）转化为T3无关。甲状腺切除的大鼠给予替代剂量的T3（0.5 mg kg（-1）p.o.每日一次，持续3天），与或不与胺碘酮（50 mg/kg（-1）p.o.每天一次，持续1周）。2如通过RT-PCR所评估的，用T3治疗甲状腺切除大鼠引起β 3-肾上腺素受体减少2倍使用[H-3]-CGP 12177作为配体的结合研究表明，T3治疗甲状腺切除大鼠导致β 3-AR mRNA水平降低70%，β 1-AR mRNA水平增加2倍。AR数量和BAT膜中β 1-AR增加80%。4 T3治疗消除了CGP 12177诱导的甲状腺切除大鼠BAT腺苷酸环化酶（AC）活性增加。它还使G（i）蛋白（ADP-核糖基化）的量减少了30%。5与心脏文献不同，胺碘酮给药并未抑制甲状腺切除大鼠BAT中T3对β 1-AR表达的积极作用。然而，它拮抗了T3对β 3-AR数量的影响，但不拮抗AC活性或G（i）表达。6这些结果表明，甲状腺激素对BAT对儿茶酚胺的反应性的影响涉及受体和受体后机制，它们还表明胺碘酮和甲状腺激素之间的相互作用具有高度组织特异性，并取决于β-AR亚型。
1 This study was undertaken to evaluate in vivo the influence of amiodarone on the effects of triiodothyronine (T3) in brown adipose tissue (BAT) which are independent of thyroid hormone synthesis and of the conversion of thyroxine (T4) to T3. Thyroidectomized rats were given a replacement dose of T3 (0.5 mg kg(-1) p.o. daily for 3 days) with or without amiodarone (50 mg kg(-1) p.o. daily for 1 week).2 As assessed by RT - PCR, treatment of thyroidectomized rats with T3 caused 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 of thyoidectomized rats with T3 resulted in a 70% decrease in beta 3-AR number 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 did 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-AR number, but not on AC activity or on G(i) expression.6 These results indicate that the effects of thyroid hormones on the responsiveness of BAT to catecholamines involves both receptor and post-receptor mechanisms, they also suggest that interaction between amiodarone and thyroid hormones is highly tissue-specific and depends on the beta-AR subtype.