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Am J Physiol Regul Integr Comp Physiol 275: R2002-R2011, 1998;
0363-6119/98 $5.00
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Vol. 275, Issue 6, R2002-R2011, December 1998

Thermogenesis is beta 3- but not beta 1-adrenergically mediated in rat brown fat cells, even after cold acclimation

Jin Zhao, Barbara Cannon, and Jan Nedergaard

The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, S-106 91 Stockholm, Sweden

To examine if acclimation of rats to cold led to alterations in the coupling between different beta -receptor subtypes and thermogenesis in brown fat cells, we investigated the adrenergic response patterns in brown fat cells isolated from warm-acclimated (28°C) and cold-acclimated (4°C) rats. In the cells from warm-acclimated rats, the relative affinities (EC50) for different agonists (isoprenaline, BRL-37344, norepinephrine, CGP-12177, dobutamine, and salbutamol) were those expected from their interaction with a beta 3-receptor. The response to norepinephrine was competitively inhibited by propranolol with a pA2 of approx 6, implying interaction at the beta 3-receptor. No evidence for a beta 1-receptor-mediated response to the beta 1-selective agonist dobutamine could be obtained; the low-affinity response observed was most likely through the beta 3-receptor. The beta 1-antagonist ICI-89406 could not inhibit a specific fraction of the thermogenic response to norepinephrine. Thus beta 3-receptors were the only beta -receptors involved in the control of thermogenesis in brown fat cells from warm-acclimated rats. A modified method of preparation was developed to isolate functional cells from cold-acclimated animals. Also in these cells, the beta -receptor coupled to thermogenesis was the beta 3-receptor, although the response was desensitized with an approximately sevenfold shift in EC50 values. The pA2 for propranolol inhibition of norepinephrine-induced thermogenesis was also 6 here, and that for ICI-89406 was 5.5, also implying interaction at the beta 3-receptor. Thus acclimation to cold did not alter the beta -adrenergic receptor subtype (beta 3) involved in the control of thermogenesis.

norepinephrine; BRL-37344; CGP-12177; dobutamine; salbutamol


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