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) 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.
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Laboratoire de Pharmacologie Clinique et Expérimentale, Université Paris Nord, Bobigny, France. rbazin@bhdc.jussiev.fr
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D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004347:Drug Interactions; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000187:drug effects / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011412:Propanolamines / Q000494:pharmacology; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000235:genetics*; D014284:Triiodothyronine / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D011412:Propanolamines; D011506:Proteins; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D000638:Amiodarone; C033394:CGP 12177