Opposing effects of activation of central GABAA and GABAB receptors on brown fat thermogenesis in the rat.
Baclofen (a GABAB agonist) stimulates body temperature, metabolic rate and brown adipose tissue (BAT) in the rat through a central action, but no effects of gamma-aminobutyric acid (GABA) itself on these parameters were observed. In the present study, it was found that the central effects of (+/-)baclofen (0.5-2.0 micrograms injection i.c.v.) on the temperature (1.2 degrees C increase) and metabolic rate (44-76% increase) of brown adipose tissue were inhibited by previous treatment with the GABAA agonist, muscimol (0.05 micrograms). Injection of GABA alone (12 micrograms) did not significantly affect these parameters, but in the presence of the GABAA antagonist bicuculline (2.5 micrograms), GABA significantly increased the temperature (0.3 degrees C) and oxygen consumption (22%) of brown fat. (-)Baclofen was found to be approximately 50-times more effective in stimulating the temperature of brown adipose tissue than (+/-)baclofen. The results indicate that activation of central GABAB receptors stimulates the activity and hence metabolic rate of brown adipose tissue. However, activation of the GABAA receptors opposes the effects of GABAB stimulation on the thermogenesis of brown fat.
Horton
R W
RW
Department of Pharmacology, St. George's Hospital Medical School, Tooting, London.
LeFeuvre
R A
RA
Rothwell
N J
NJ
Stock
M J
MJ
D002001:Adipose Tissue, Brown / Q000502:physiology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001833:Body Temperature Regulation / Q000187:drug effects*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*
D011963:Receptors, GABA-A; D011433:Propranolol; D001418:Baclofen