scholarly journals The β-adrenergic radioligand [3H]CGP-12177, generally classified as an antagonist, is a thermogenic agonist in brown adipose tissue

1989 ◽  
Vol 261 (2) ◽  
pp. 401-405 ◽  
Author(s):  
N Mohell ◽  
A Dicker
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Maximal Effect ◽  
Binding Studies ◽  
Isolated Cells ◽  
High Affinity ◽  
Brown Adipose ◽  
High Affinity Binding Site ◽  
Cgp 12177 ◽  
The One

The effect of CGP-12177, originally developed as a radioligand with antagonist properties for binding studies of beta-adrenergic receptors, was investigated in brown adipose tissue. Contrary to expectations, CGP-12177 showed clear agonist properties in experiments with hamster brown-fat cells, with a maximal effect in stimulating oxygen consumption similar to that of the physiological stimulator noradrenaline, and also with a potency similar to that of noradrenaline [EC50 (50% effective concn.) approx. 70 nM]. This value could be contrasted with the very high affinity of CGP-12177 (KD about 1 nM) for ligand-binding sites on the cells. It is therefore suggested that the high-affinity binding site may not be the one that mediates the CGP-12177-stimulated thermogenesis in isolated cells. Also, when injected into cold-adapted rats, CGP-12177 stimulated non-shivering thermogenesis similarly to noradrenaline. This observation, in conjunction with the reported low general sympathomimetic effect of CGP-12177, may indicate that CGP-12177 could be of interest for the development of anti-obesity drugs.

scholarly journals Regulation of Na+ transport in brown adipose tissue

1986 ◽  
Vol 235 (2) ◽  
pp. 545-552 ◽  
Author(s):  
K F LaNoue ◽  
C Koch ◽  
D Strzelecka ◽  
T P Kobylski
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Membrane Vesicle ◽  
Membrane Vesicles ◽  
Fat Cell ◽  
Isolated Cells ◽  
Intact Cells ◽  
Dependent Atpase ◽  
Brown Adipose ◽  
Active Transport System

In order to test the hypothesis that Na+, K+-ATPase (Na+,K+-dependent ATPase) is involved in the noradrenaline-mediated stimulation of respiration in brown adipose tissue, the effects of noradrenaline on Na+,K+-ATPase in isolated brown-fat-cell membrane vesicles, and on 22Na+ and K+ (86Rb+) fluxes across the membranes of intact isolated cells, were measured. The ouabain-sensitive fraction of the K+-dependent ATPase activity in the isolated membrane-vesicle preparation was small and was not affected by the presence of noradrenaline in the incubation media. The uptake of 86Rb+ into intact hormone-sensitive cells was inhibited by 80% by ouabain, but it was insensitive to the presence of noradrenaline. 22Na+ uptake and efflux measured in the intact cells were 8 times more rapid than the 86Rb+ fluxes and were unaffected by ouabain. This indicated the presence of a separate, more active, transport system for Na+ than the Na+,K+-ATPase. This is likely to be a Na+/Na+ exchange activity under normal aerobic conditions. However, under anaerobic conditions, or conditions simulating anaerobiosis (2 mM-NaCN), the unidirectional uptake of Na+ increased dramatically, while efflux was unaltered.

Effects of triiodothyronine administration on the adenylyl cyclase system in brown adipose tissue of rat

1997 ◽  
Vol 273 (2) ◽  
pp. E247-E253
Author(s):  
H. Adli ◽  
R. Bazin ◽  
R. Vassy ◽  
G. Y. Perret
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Adenylyl Cyclase ◽  
Protein Concentration ◽  
Response Curves ◽  
Fourfold Increase ◽  
Brown Adipose ◽  
Cgp 12177 ◽  
Polymerase Chain ◽  
Gamma S

This study was undertaken to investigate the effect of triiodothyronine (T3) administration to euthyroid rats on beta 3-adrenoceptor (beta 3-AR) expression and on the different components of the adenylyl cyclase (AC) system in brown adipose tissue (BAT). In rats treated with T3, the beta 3-AR density (assessed by the binding of [3H]CGP-12177) showed a decrease of 50%, as did their mRNA, as analyzed by reverse transcriptase-polymerase chain reaction. In hyperthyroid rats, compared with control rats, there was a 40% increase in G alpha s activity (stimulated by NaF or GTP gamma S) and a fourfold increase in the protein concentration (Western blotting). In contrast, the level of the pertussis toxin substrate Gi declined by 35% in response to T3. Analysis of dose-response curves for isoproterenol and CGP-12177 revealed that neither basal nor stimulated AC activities nor 50% stimulatory concentration for these agonists was changed by T3 administration. In conclusion, these results suggest that downregulation of the beta 3-AR by T3 was counter-balanced by changes in other components of the AC cascade (i.e., Gs and Gi), so no change occurred in the capacity of BAT to generate adenosine 3',5'-cyclic monophosphate.

scholarly journals Cold exposure regulates the norepinephrine uptake transporter in rat brown adipose tissue

1999 ◽  
Vol 276 (1) ◽  
pp. R143-R151 ◽  
Author(s):  
Victoria L. King ◽  
Linda P. Dwoskin ◽  
Lisa A. Cassis
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Kinetic Parameters ◽  
Cold Exposure ◽  
Time Course ◽  
Neuronal Uptake ◽  
Interscapular Brown Adipose Tissue ◽  
High Affinity ◽  
Brown Adipose ◽  
And Control

The neuronal uptake of norepinephrine (NE) in sympathetically innervated tissues is mediated by a high-affinity NE uptake transporter (NET). Rat interscapular brown adipose tissue (ISBAT) is densely innervated by the sympathetic nervous system for the control of cold- and diet-induced thermogenesis. To determine if cold exposure regulates the NET, kinetic parameters for [3H]NE uptake and [3H]nisoxetine (Nis) binding were determined in ISBAT from 7-day cold-exposed (CE) and control rats. Uptake of [3H]NE in ISBAT slices was of high affinity (1.6 μM). After 7 days of cold exposure the affinity for [3H]NE uptake was not altered; however, the uptake capacity was decreased (38%) in ISBAT slices from CE rats. Kinetic parameters for [3H]Nis binding demonstrated a single high-affinity site in ISBAT from CE and control rats with similar affinity. The density of [3H]Nis sites in ISBAT was decreased (38%) following cold exposure. A time course (2 h-7 days) for cold exposure demonstrated downregulation of [3H]Nis binding density by day 3, which remained through day 7. The affinity for [3H]Nis binding was transiently decreased at 2 h of cold exposure. Similarly, ISBAT NE content was decreased at 2 h of cold exposure. Pair feeding CE rats to food intake of controls normalized plasma NE content; however, [3H]Nis binding density in ISBAT remained decreased in pair-fed rats. These results demonstrate that the ISBAT NET is downregulated following cold exposure. Reductions in ISBAT NE content precede alterations in NET density; however, plasma NE content is not related to regulation of the NET.

scholarly journals Retrieval of precursors for white-type adipose conversion in brown adipose tissue

1988 ◽  
Vol 255 (3) ◽  
pp. 849-854 ◽  
Author(s):  
C M Poissonnet ◽  
M Ouagued ◽  
Y Aron ◽  
J Y Pello ◽  
E Swierczewski ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Gradient Centrifugation ◽  
Cellular Compartment ◽  
Percoll Density Gradient Centrifugation ◽  
Brown Adipose ◽  
Adipose Conversion ◽  
Percoll Density Gradient ◽  
The One

A cellular compartment from brown adipose tissue (BAT) of newborn rats was isolated by Percoll-density-gradient centrifugation and was shown to proliferate and to undergo adipose conversion in vitro in primary culture. The features of the effector requirement for adipose conversion as well as the differentiated morphological and biochemical phenotype are almost identical with that of a compartment designated HCF, from white adipose tissue (WAT). A possible role for these precursors from BAT and WAT in the involution of BAT into WAT, on the one hand, and in the development of brown adipose cells among typical WAT deposits, on the other, is discussed.

scholarly journals Regulation of rat foetal lipogenesis in brown adipose tissue in vivo and in isolated brown adipocytes during the last day of, and after prolonged, gestation

1987 ◽  
Vol 243 (2) ◽  
pp. 617-620 ◽  
Author(s):  
C Roncero ◽  
M Lorenzo ◽  
M Benito
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Incubation Medium ◽  
Brown Adipocyte ◽  
Isolated Cells ◽  
Pregnant Rats ◽  
Brown Adipocytes ◽  
Brown Adipose

Rates of lipogenesis in foetal isolated brown adipocytes from 22-day-pregnant rats were significantly increased by lactate plus pyruvate as major substrates in the incubation medium, in comparison with the endogenous rates. Insulin stimulated foetal brown-adipocyte lipogenesis, and adrenaline or noradrenaline and isoprenaline decreased lipogenesis. Glucagon had no effect on the lipogenic rate in brown adipocytes. Progesterone administration to the mother significantly increased the rates of lipogenesis in brown adipose tissue and in isolated brown adipocytes from 22-day foetuses. Prolongation of gestation by progesterone to day 23 decreased the rates of brown-adipose-tissue lipogenesis in vivo and in isolated cells in the post-mature foetuses.

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