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Triiodothyronine and amiodarone effects on β 3 ‐adrenoceptor density and lipolytic response to the β 3 ‐adrenergic agonist BRL 37344 in rat white adipocytes
Author(s) -
Germack R.,
Adli H.,
Vassy R.,
Perret GY
Publication year - 1996
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1996.tb00308.x
Subject(s) - endocrinology , medicine , lipolysis , triiodothyronine , agonist , beta 3 adrenergic receptor , receptor , chemistry , adipose tissue , hormone , beta (programming language) , white adipose tissue , adrenergic receptor , biology , computer science , programming language
Summary— The β‐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 (T 3 ) effect on β‐adrenergic receptors (β‐ARs) in adipose tissue. AM decreases the expression of some T 3 sensitive genes in various tissues and antagonizes the effect of T 3 on its nuclear receptors. In this study, the T 3 , AM and AM + T 3 effects on the β1‐ and β 3 ‐AR density were assessed on rat white adipocytes by radioligand binding using [ 3 H]CGP 12177 after characterization of these subtypes by displacement of [ 3 H]CGP 12177 binding by isoproterenol, BRL 37344 and noradrenaline. BRL 37344 was used to study β 3 ‐AR lipolysis. White adipocytes from hyperthyroid rats had increased responsiveness (E max × 2) and sensitivity (+ 38%) to BRL 37344, while those given AM alone had decreased values. Moreover, AM antagonized the T 3 effect on lipolysis. The β 1 ‐binding characteristics (receptor density [B max ]: 45 ± 4 fmol/mg of proteins; dissociation factor [K d ]: 0.96 ± 0.10 nM) were not modified by either compound. Finally, T 3 significantly increased β 3 ‐AR density (587 ± 69 versus 363 ± 25 fmol/mg of proteins) and K d (38 ± 2 versus 23 ± 3 nM), while AM alone had no effect and did not antagonize the T 3 effect on β 3 ‐AR number. In conclusion, the hyperthyroid state in the rat potentiated the lipolytic response of white adipocytes to a specific β 3 ‐agonist and increased the β 3 ‐AR density without changing in β 1 ‐AR number and affinity. Furthermore, the lack of antagonism between AM and T 3 on β 3 ‐AR expression suggests that T 3 does not work directly on the β 3 ‐AR gene. Moreover, AM induced a functional tissular hypothyroid‐like effect and its antilipolytic effect probably occurred at a postreceptor level.