Thermogenesis is beta3- but not beta1-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 degreesC) and cold-acclimated (4 degreesC) 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 beta3-receptor. The response to norepinephrine was competitively inhibited by propranolol with a pA2 of approximately 6, implying interaction at the beta3-receptor. No evidence for a beta1-receptor-mediated response to the beta1-selective agonist dobutamine could be obtained; the low-affinity response observed was most likely through the beta3-receptor. The beta1-antagonist ICI-89406 could not inhibit a specific fraction of the thermogenic response to norepinephrine. Thus beta3-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 beta3-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 beta3-receptor. Thus acclimation to cold did not alter the beta-adrenergic receptor subtype (beta3) involved in the control of thermogenesis.
Zhao
J
J
The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, S-106 91 Stockholm, Sweden.
Cannon
B
B
Nedergaard
J
J
D000064:Acclimatization / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000502:physiology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D002469:Cell Separation; D003080:Cold Temperature; D005260:Female; D006358:Hot Temperature; D008297:Male; D009638:Norepinephrine / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine