Triiodothyronine and amiodarone effects on beta 3-adrenoceptor density and lipolytic response to the beta 3-adrenergic agonist BRL 37344 in rat white adipocytes.
The beta-adrenergic effects of catecholamines are potentiated by thyroid hormones in adipose tissue. Amiodarone (AM) is structurally similar to thyroid hormones and was used to explore the mechanism of the triiodothyronine (T3) effect on beta-adrenergic receptors (beta-ARs) in adipose tissue. AM decreases the expression of some T3 sensitive genes in various tissues and antagonizes the effect of T3 on its nuclear receptors. In this study, the T3, AM and AM + T3 effects on the beta 1- and beta 3-AR density were assessed on rat white adipocytes by radioligand binding using [3H]CGP 12177 after characterization of these subtypes by displacement of [3H]CGP 12177 binding by isoproterenol, BRL 37344 and noradrenaline. BRL 37344 was used to study beta 3-AR lipolysis. White adipocytes from hyperthyroid rats had increased responsiveness (Emax x 2) and sensitivity (+ 38%) to BRL 37344, while those given AM alone had decreased values. Moreover, AM antagonized the T3 effect on lipolysis. The beta 1-binding characteristics (receptor density [Bmax]: 45 +/- 4 fmol/mg of proteins; dissociation factor [Kd]: 0.96 +/- 0.10 nM) were not modified by either compound. Finally, T3 significantly increased beta 3-AR density (587 +/- 69 versus 363 +/- 25 fmol/mg of proteins) and Kd (38 +/- 2 versus 23 +/- 3 nM), while AM alone had no effect and did not antagonize the T3 effect on beta 3-AR number. In conclusion, the hyperthyroid state in the rat potentiated the lipolytic response of white adipocytes to a specific beta 3-agonist and increased the beta 3-AR density without changing in beta 1-AR number and affinity. Furthermore, the lack of antagonism between AM and T3 on beta 3-AR expression suggests that T3 does not work directly on the beta 3-AR gene. Moreover, AM induced a functional tissular hypothyroid-like effect and its antilipolytic effect probably occurred at a postreceptor level.
Germack
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R
Département de Biophysique et de Pharmacologie des Biosignaux, Faculté de Médecine, Université Paris-Nord, Bobigny, France.
Adli
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H
Vassy
R
R
Perret
G Y
GY
D017667:Adipocytes / Q000201:enzymology / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000378:metabolism* / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000638:Amiodarone / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000378:metabolism* / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology; D008297:Male; D011412:Propanolamines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D014284:Triiodothyronine / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; C057368:BRL 37344; D000638:Amiodarone; C033394:CGP 12177