Adenosine receptor down-regulation and insulin resistance following prolonged incubation of adipocytes with an A1 adenosine receptor agonist.

Green, A

doi:10.1016/s0021-9258(18)47784-8

Cited by 132 publications

(9 citation statements)

References 40 publications

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“…Apparent concurrent down-regulation in rat adipocytes in primary culture of Al adenosine receptors with a number of pertussis-toxin-sensitive G-proteins has been recorded previously [17,32], although this process is considerably slower than the effects noted herein. Loss of the 'Gi-like' G-proteins in such cells has been noted to be associated with the development of heterologous desensitization of the action of anti-lipolytic hormones [33], and, although alterations of steady-state levels of Gsa have also been recorded [8,13] in NG108-15 cells, this is the first report to demonstrate the temporal concurrence of loss of G,a and of a receptor which interacts with this G-protein.…”

Section: Controlsupporting

confidence: 58%

Concurrent down-regulation of IP prostanoid receptors and the α-subunit of the stimulatory guanine-nucleotide-binding protein (Gs) during prolonged exposure of neuroblastoma × glioma cells to prostanoid agonists. Quantification and functional implications

Adie

Mullaney

McKenzie

et al. 1992

Biochemical Journal

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Neuroblastoma x glioma hybrid NG108-15 cells express a high-affinity IP prostanoid receptor. Saturation binding analysis of this receptor, using [3H]prostaglandin E1 ([3H]PGE1) as ligand, indicated that it was present at some 1.5 pmol/mg of membrane protein and displayed a dissociation constant for this ligand of 30-40 nM. Prolonged exposure of these cells either to PGE1 or to iloprost, which is a stable analogue of prostacyclin, caused a 40-70% decrease in levels of the receptor. The remaining receptors were capable of interacting with the stimulatory G-protein (Gs) of the adenylate cyclase cascade, as saturation analysis of the binding of [3H]PGE1 indicated that they had a similar affinity for the 3H-labelled ligand, and because the specific binding of [3H]PGE1 to these receptors was still sensitive to the presence of poorly hydrolysed analogues of GTP. We have recently demonstrated that prolonged exposure of NG108-15 ells to PGE1 causes a cyclic AMP-independent loss of Gs alpha-subunit (Gs alpha) from these cells [McKenzie & Milligan (1990) J. Biol. Chem. 265, 17084-17093]. Steady-state concentration of the larger 45 kDa form of Gs alpha (which is the predominant form expressed in these cells) was assessed to be 9.6 pmol/mg of membrane protein, and treatment with iloprost decreased levels of this polypeptide to some 3.0 pmol/mg of protein. Time courses of iloprost-mediated down-regulation of the IP prostanoid receptor, loss of Gs alpha protein as assessed by immunoblotting and loss of Gs alpha activity as assessed by the reconstitution of NaF stimulation of adenylate cyclase activity to membranes of S49 cyc- cells by sodium cholate extracts of NG108-15 cells were identical, suggesting that the loss of the IP prostanoid receptor and G-protein occurred in parallel. Each of these effects was half-maximal between 2 and 3 h of exposure to the agonist. Stoichiometry of loss of Gs alpha and IP prostanoid receptor was unchanged by the percentage receptor occupancy, and quantification indicated the loss of some 7-10 mol of Gs alpha/mol of receptor. This is the first report to demonstrate the temporal concurrence of loss of Gs alpha and of a receptor which interacts with this G-protein. Chronic activation of the IP prostanoid receptor on these cells results in the development of a heterologous form of desensitization to agents which function to activate adenylate cyclase [Kelly, Keen, Nobbs & MacDermot (1990) Br. J. Pharmacol. 99, 306-316]. Agonist regulation of Gs alpha levels in these cells may contribute to this process.

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Section: Controlsupporting

confidence: 58%

Concurrent down-regulation of IP prostanoid receptors and the α-subunit of the stimulatory guanine-nucleotide-binding protein (Gs) during prolonged exposure of neuroblastoma × glioma cells to prostanoid agonists. Quantification and functional implications

Adie

Mullaney

McKenzie

et al. 1992

Biochemical Journal

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“…However, their risk factors may themselves affect haemodynamic response to adenosine. The A1 adenosine receptor responsible for splenic vasoconstriction is also complicit in insulin resistance and the downregulation of adenosine receptors has been implicated in insulin insensitivity 16 . Hypercholesterolaemia, chronic hypertension and family history have also been linked to attenuated vascular response to adenosine, both in cellular and in-vivo studies 17,18 .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of splenic switch off in a tertiary imaging centre: validation and assessment of utility

Hosking

Koulouroudias

Zemrak

et al. 2016

European Heart Journal - Cardiovascular Imaging

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“…In adipocytes, adenosine binds to the adenosine A 1 receptor and inhibits adenylyl cyclase and thus lipolytic activity. In vitro and in vivo findings demonstrate that adenosine A 1 receptor downregulation can occur in response to elevated extracellular adenosine (12,14,26). In the present study, differences in extracellular adenosine between treatments were not observed under basal conditions but only on in vivo infusion of epinephrine or epinephrine plus dipyridamole in restricted-fed exercised swine.…”

Section: Discussionmentioning

confidence: 99%

Cellular adaptations in fat tissue of exercise-trained miniature swine: role of excess energy intake

Carey

2000

Journal of Applied Physiology

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This study examined the influence of energy expenditure and energy intake on cellular mechanisms regulating adipose tissue metabolism. Twenty-four swine were assigned to restricted-fed sedentary, restricted-fed exercise-trained, full-fed sedentary, or full-fed exercise-trained groups. After 3 mo of treatment, adipocytes were isolated and adipocyte size, adenosine A(1) receptor characteristics, and lipolytic sensitivity were measured. Swine were infused with epinephrine during which adipose tissue extracellular adenosine, plasma fatty acids, and plasma glycerol were measured. Results revealed that adipocytes isolated from restricted-fed exercised swine had a smaller diameter, a lower number of A(1) receptors, and a greater sensitivity to lipolytic stimulation, compared with adipocytes from full-fed exercised swine. Extracellular adenosine levels were transiently increased on infusion of epinephrine in adipose tissue of restricted-fed exercised but not full-fed exercised swine. These results suggest a role for adenosine in explaining the discrepancy between in vitro and in vivo lipolysis findings and underscore the notion that excess energy intake dampens the lipolytic sensitivity of adipocytes to beta-agonists and adenosine, even if accompanied by exercise training.

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Adenosine receptor down-regulation and insulin resistance following prolonged incubation of adipocytes with an A1 adenosine receptor agonist.

Cited by 132 publications

References 40 publications

Concurrent down-regulation of IP prostanoid receptors and the α-subunit of the stimulatory guanine-nucleotide-binding protein (Gs) during prolonged exposure of neuroblastoma × glioma cells to prostanoid agonists. Quantification and functional implications

Concurrent down-regulation of IP prostanoid receptors and the α-subunit of the stimulatory guanine-nucleotide-binding protein (Gs) during prolonged exposure of neuroblastoma × glioma cells to prostanoid agonists. Quantification and functional implications

Evaluation of splenic switch off in a tertiary imaging centre: validation and assessment of utility

Cellular adaptations in fat tissue of exercise-trained miniature swine: role of excess energy intake

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