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Metabolic response to various β ‐adrenoceptor agonists in β 3 ‐adrenoceptor knockout mice: Evidence for a new β ‐adrenergic receptor in brown adipose tissue
Author(s) -
Preitner Frédéric,
Muzzin Patrick,
Revelli JeanPierre,
Seydoux Josiane,
Galitzky Jean,
Berlan Michel,
Lafontan Max,
Giacobino JeanPaul
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702007
Subject(s) - adrenergic receptor , endocrinology , adipose tissue , medicine , brown adipose tissue , adrenergic , receptor , knockout mouse , isoprenaline , biology , chemistry , stimulation
The β 3 ‐adrenoceptor plays an important role in the adrenergic response of brown and white adipose tissues (BAT and WAT). In this study, in vitro metabolic responses to β‐adrenoceptor stimulation were compared in adipose tissues of β 3 ‐adrenoceptor knockout and wild type mice. The measured parameters were BAT fragment oxygen uptake (MO 2 ) and isolated white adipocyte lipolysis. In BAT of wild type mice (−)‐norepinephrine maximally stimulated MO 2 4.1±0.8 fold. Similar maximal stimulations were obtained with β 1 ‐,β 2 ‐ or β 3 ‐adrenoceptor selective agonists (dobutamine 5.1±0.3, terbutaline 5.3±0.3 and CL 316,243 4.8±0.9 fold, respectively); in BAT of β 3 ‐adrenoceptor knockout mice, the β 1 ‐ and β 2 ‐responses were fully conserved. In BAT of wild type mice, the β 1 /β 2 ‐antagonist and β 3 ‐partial agonist CGP 12177 elicited a maximal MO 2 response (4.7±0.4 fold). In β 3 ‐adrenoceptor knockout BAT, this response was fully conserved despite an absence of response to CL 316,243. This unexpected result suggests that an atypical β‐adrenoceptor, distinct from the β 1 ‐, β 2 ‐ and β 3 ‐subtypes and referred to as a putative β 4 ‐adrenoceptor is present in BAT and that it can mediate in vitro a maximal MO 2 stimulation. In isolated white adipocytes of wild type mice, (−)‐epinephrine maximally stimulated lipolysis 12.1±2.6 fold. Similar maximal stimulations were obtained with β 1 ‐, β 2 ‐ or β 3 ‐adrenoceptor selective agonists (TO509 12±2, procaterol 11±3, CL 316,243 11±3 fold, respectively) or with CGP 12177 (7.1±1.5 fold). In isolated white adipocytes of β 3 ‐adrenoceptor knockout mice, the lipolytic responses to (−)epinephrine, to the β 1 ‐, β 2 ‐, β 3 ‐adrenoceptor selective agonists and to CGP 12177 were almost or totally depressed, whereas those to ACTH, forskolin and dibutyryl cyclic AMP were conserved.British Journal of Pharmacology (1998) 124 , 1684–1688; doi: 10.1038/sj.bjp.0702007