Thermogenesis is β3- but not β1-adrenergically mediated in rat brown fat cells, even after cold acclimation.

To examine if acclimation of rats to cold led to alterations in the coupling between different β-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 β3-receptor. The response to norepinephrine was competitively inhibited by propranolol with a p A 2of ≈6, implying interaction at the β3-receptor. No evidence for a β1-receptor-mediated response to the β1-selective agonist dobutamine could be obtained; the low-affinity response observed was most likely through the β3-receptor. The β1-antagonist ICI-89406 could not inhibit a specific fraction of the thermogenic response to norepinephrine. Thus β3-receptors were the only β-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 β-receptor coupled to thermogenesis was the β3-receptor, although the response was desensitized with an approximately sevenfold shift in EC50 values. The p A 2for propranolol inhibition of norepinephrine-induced thermogenesis was also 6 here, and that for ICI-89406 was 5.5, also implying interaction at the β3-receptor. Thus acclimation to cold did not alter the β-adrenergic receptor subtype (β3) involved in the control of thermogenesis.