胺碘酮与三碘甲状腺原氨酸对大鼠棕色脂肪组织中β-肾上腺素能受体表达的相互作用。

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

作者信息

Adli H, Bazin R, Perret G Y

机构信息

Laboratoire de Pharmacologie Clinique et Expérimentale, Université Paris Nord, Bobigny, France.

出版信息

Br J Pharmacol. 1999 Mar;126(6):1455-61. doi: 10.1038/sj.bjp.0702456.

DOI:10.1038/sj.bjp.0702456

PMID:10217540

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565924/

Abstract

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 beta3-adrenoceptor (beta3-AR) mRNA levels and a 2 fold increase in beta1-AR mRNA levels. 3. Binding studies using [3H]-CGP 12177 as a ligand showed that treatment of thyoidectomized rats with T3 resulted in a 70% decrease in beta3-AR number and in an 80% increase in beta1-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 Gi 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 beta1-AR expression in BAT in thyroidectomized rats. However, it antagonized the effect of T3 on beta3-AR number, but not on AC activity or on Gi 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.

摘要

本研究旨在体内评估胺碘酮对棕色脂肪组织（BAT）中三碘甲状腺原氨酸（T3）作用的影响，这些作用独立于甲状腺激素合成以及甲状腺素（T4）向T3的转化。对甲状腺切除的大鼠给予T3替代剂量（每天口服0.5 mg kg⁻¹，共3天），同时或不同时给予胺碘酮（每天口服50 mg kg⁻¹，共1周）。2. 通过逆转录聚合酶链反应（RT-PCR）评估，用T3治疗甲状腺切除的大鼠导致β3-肾上腺素能受体（β3-AR）mRNA水平降低2倍，β1-AR mRNA水平升高2倍。3. 使用[³H]-CGP 12177作为配体的结合研究表明，用T3治疗甲状腺切除的大鼠导致BAT膜中β3-AR数量减少70%，β1-AR增加80%。4. T3治疗消除了甲状腺切除大鼠中CGP12177诱导的BAT腺苷酸环化酶（AC）活性增加。它还使Gi蛋白（ADP-核糖基化）量减少了3０%。5. 与关于心脏的文献不同，给予胺碘酮并未抑制T3对甲状腺切除大鼠BAT中β1-AR表达的积极作用。然而，它拮抗了T3对β3-AR数量的作用，但对AC活性或Gi表达无影响。6. 这些结果表明，甲状腺激素对BAT对儿茶酚胺反应性的影响涉及受体和受体后机制，它们还表明胺碘酮与甲状腺激素之间的相互作用具有高度的组织特异性，并取决于β-AR亚型。