The molecular basis for adrenergic desensitization in hamster brown adipose tissue: Uncoupling of adenylate cyclase activation

Svartengren, Jan; Svoboda, Petr; Drahota, Z; Cannon, Barbara

doi:10.1016/0742-8413(84)90064-1

Cited by 9 publications

(8 citation statements)

References 28 publications

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“…Under these conditions, the number of specific [ 3 H]dihydroalprenolol binding sites was decreased by 34%. Similar data were obtained on 3 times washed crude membranes (sediment 100 000 g) (Svartengren et al 1984). Throughout the years, we have tried to improve this isolation procedure.…”

Section: Purification Of Plasma Membranes From Batsupporting

confidence: 62%

“…3A) This surprising result, when related to our previously published data (Svartengren et al 1984, Svoboda et al 1984b, was verified in a highly representative set of 32 independent gradient purified plasma membrane preparations (16 from controls and 16 from cold-acclimated animals). To compare the specific [ 3 H]CGP12177 binding in all these membranes, a single concentration (30 nM) of this radioligand was used.…”

Section: [ 3 H]cgp12177 Bindingmentioning

confidence: 50%

“…The decrease in G s proteins proceeds preferentially as a decrease in the short variant of G s . From the functional point of view, the cold-induced desensitisation of BAT (Freidli et al 1978, Nedergaard 1982, Svartengren et al 1982, Svartengren et al 1984, Unnelius 1990, Kuroshima et al 1991 is associated with decreased beta-adrenergic responsiveness of adenylyl cyclase and by decreased functional activity of G s proteins (Svoboda et al 1993).…”

Section: Purification Of Plasma Membranes From Batmentioning

confidence: 99%

“…This is because brown adipose tissue is constantly stimulated by norepinephrine when the animal is exposed to cold (Feist 1970, Sigurdson & Himms-Hagen 1988. The cells (Nedergaard 1982, Svartengren et al 1982, Unnelius 1990, tissue pieces (Freidli et al 1978, Kuroshima et al 1991, crude membranes (Svartengren et al 1984) or plasma membrane-enriched fractions (Svoboda et al 1984a(Svoboda et al , 1993 prepared from brown adipose tissue of coldacclimated animals have a decreased respiratory (Nedergaard 1982, Svartengren et al 1982, Unnelius 1990, cAMP (Svartengren et al 1982), adenylyl cyclase (Svartengren et al 1984, Svoboda et al 1984a or thermogenic (Freidli et al 1978) response to -adrenergic stimulation.…”

Section: Introductionmentioning

confidence: 99%

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The decrease in the short variant of gsalpha protein is associated with an increase in [3H]CGP12177 binding, [3H]ouabain binding and Na, K-ATPase activity in brown adipose tissue plasma membranes of cold-acclimated hamsters

Bouřová

Novotn²,

Svoboda³

1999

Journal of Molecular Endocrinology

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Sucrose density gradient purified plasma membranes isolated from brown adipose tissue of cold-acclimated hamsters (4-10 weeks at 0-4 C) were analysed for the content of the short (G s S) and long (G s L) variants of G s protein (the subunit of the stimulatory G protein) and compared with the membranes isolated from control animals. The relative ratio between the two variants (G s S/G s L) decreased from 0·48 to 0·24 (P<0·01). This result, obtained by electrophoretic resolution of membrane proteins by standard SDS-PAGE and an immunoblot analysis with an antiserum oriented against an internal sequence of G s , was verified by resolution on urea-containing gels and an antiserum oriented against the C-terminus decapeptide of G s .Under these conditions, the G s S/G s L ratio was decreased from 0·41 to 0·31 (P<0·05). The total amount of both isoforms (G s S plus G s L) decreased to 83% (P<0·05) or 68% (P<0·01) by standard or urea SDS-PAGE respectively. These data demonstrate that cold-acclimation of hamster brown adipose tissue is associated with preferential decrease in the plasma membrane density of the short variant of the G s protein.This decrease was paralleled by an increase in the other plasma membrane constituents, [ 3 H]CGP12177 binding sites, [3 H]ouabain binding sites and Na,K-ATPase activity to 147%, 212% and 191% respectively.

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Section: Purification Of Plasma Membranes From Batsupporting

confidence: 62%

Section: [ 3 H]cgp12177 Bindingmentioning

confidence: 50%

Section: Purification Of Plasma Membranes From Batmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The decrease in the short variant of gsalpha protein is associated with an increase in [3H]CGP12177 binding, [3H]ouabain binding and Na, K-ATPase activity in brown adipose tissue plasma membranes of cold-acclimated hamsters

Bouřová

Novotn²,

Svoboda³

1999

Journal of Molecular Endocrinology

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“…Agonist regimes, cell types and significances of differences as in Table 2 Regime Insulin Cell type Regression coefficients ( P < 0.05) from zero, the value is given. Agonist regimes, cell types and significances of differences are as indicated in Table 2 Regime Insulin Cell type Regression coefficients ascribed to the desensitization of /?-adrenergic-receptor-linked adenylate cyclase [29]. The enhanced responsiveness of respiratory activity to noradrenaline in C cells, reported here, may be explicable in terms of the recent suggestion [28] that methods of preparation of adipocytes influence responsivity to catecholamines.…”

Section: Discussionmentioning

confidence: 62%

Modulation by insulin and glucagon of noradrenaline-induced activation of isolated brown adipocytes from the rat

Howland

Bond

1987

Eur J Biochem

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1. The effects of insulin (2 nM and 4 nM) upon oxygen consumption ( VoJ, lipolysis rates and indirectly derived rates of fatty acid utilization, by isolated brown adipocytes from warm-acclimated (W cells) and cold-acclimated (C cells) animals, induced by noradrenaline and glucagon separately and conjointly, are reported.2. Changes in interrelationships (coupling) between the parameters under different treatment regimes were assessed using bivariate regression analyses.3. Administration of glucagon with noradrenaline increased lipolysis/fatty acid utilization coupling without concomitant increase of Vo2 suggesting that glucagon may increase re-esterification through glycogenolytic generation of glycerol 3-phosphate, trapping intracellular fatty acid in excess of the capacity of disposal mechanisms, thus conserving respiratory substrate.4. W cells were unresponsive to glucagon in terms of lipolysis and po2'; C cells responded to glucagon with parallel increases in lipolysis rate and Both cell types responded to noradrenaline alone and conjointly with glucagon; C cells-were more sensitive to these agonists than W cells.5. Lipolysis/ Vo, coupling was reduced in C cells suggesting that in cold acclimation, noradrenaline-induced lipolysis rates are in excess of the capacity of cellular oxidation/re-esterification mechanisms.6. Insulin inhibited noradrenaline and glucagon-induced lipolysis, simultaneously increasing po2, supporting the hypothesis that glucose may be a thermogenic substrate in brown adipase tissue, permitting concurrent thermogenesis and lipogenesis. C cells were more insulin-sensitive than W cells.7. The data indicate that insulin may mediate its effects (additively with noradrenaline) by activation of pyruvate dehydrogenase, generating glycolytic flux and, in the presence of noradrenaline-inhibited lipogenesis, generate additional oxaloacetate, permitting increased P-oxidation.In homeotherms, non-shivering thermogenesis is mediated primarily by brown adipose tissue (BAT) [l]. The principal mechanism of activation is by means of increased sympathetic activity with liberation of noradrenaline from the dense adrenergic terminals with which the tissue is invested, and consequent activation of P-adrenergically mediated lipolysis leading to the liberation of free fatty acids from intracellular triacylglycerols. Subsequent P-oxidation of free fatty acids, associated with increased mitochondrial proton conductance induced by increased free fatty acid concentrations [2], leads to enhanced heat production by dissipation of the mitochondrial proton gradient [3]. A second effect attributed to noradrenaline release in chronic cold exposure is increased synthesis of mitochondrial protonophore [4].While noradrenaline appears to be the prime mediator of BAT thermogenesis [5], there is evidence that non-adrenergic factors such as glucagon [6, 71 may have permissive or

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Brown adipose tissue thermogenesis and obesity

Himms‐Hagen

1989

Progress in Lipid Research

317

176

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The molecular basis for adrenergic desensitization in hamster brown adipose tissue: Uncoupling of adenylate cyclase activation

Cited by 9 publications

References 28 publications

The decrease in the short variant of gsalpha protein is associated with an increase in [3H]CGP12177 binding, [3H]ouabain binding and Na, K-ATPase activity in brown adipose tissue plasma membranes of cold-acclimated hamsters

The decrease in the short variant of gsalpha protein is associated with an increase in [3H]CGP12177 binding, [3H]ouabain binding and Na, K-ATPase activity in brown adipose tissue plasma membranes of cold-acclimated hamsters

Modulation by insulin and glucagon of noradrenaline-induced activation of isolated brown adipocytes from the rat

Brown adipose tissue thermogenesis and obesity

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