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 beta-receptor subtypes and thermogenesis in brown fat cells, we investigated the adrenergic response patterns in brown fat cells isolated from warm-acclimated (28 degrees C) and cold-acclimated (4 degrees 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 Ps-receptor. The response to norepinephrine was competitively inhibited by propranolol with a pA(2) of approximate to 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 Pa-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 pA(2) 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.