Lipomobilizing effects of procaterol and yohimbine in the conscious dog: comparison of endocrinological, metabolic and cardiovascular effects

Valet, Philippe; Taouis, Mohammed; Tran, Marie-Antoinette; Montastruc, P; Lafontan, Max; Berlan, Michel

doi:10.1111/j.1476-5381.1989.tb11946.x

Cited by 15 publications

(9 citation statements)

References 40 publications

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“…In subcutaneous adipose tissue, BAR, and BAR2, but not BAR3, appear to be functionally coupled to lipolysis (7,34 (8,38,39). Furthermore, as reviewed (2), selective BAR1 resistance has been demonstrated previously in the myocardium of patients with various types ofheart failure, contrary to the present findings.…”

Section: Before Aftercontrasting

confidence: 56%

Lipolytic catecholamine resistance due to decreased beta 2-adrenoceptor expression in fat cells.

Lönnqvist

Wahrenberg²,

Hellström³

et al. 1992

J. Clin. Invest.

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The existence of lipolytic f-adrenoceptor (BAR) resistance was investigated in vivo and in isolated abdominal subcutaneous adipocytes in 65 healthy and drug-free subjects. The concentration of isoprenaline (nonselective BAR agonist) causing half-maximum lipolysis effect (EDEo) varied bimodally and 10'-fold between individuals but was almost constant in the same subject when measured two times at rest or before and 30 min after exercise. The subjects were categorized as having either high or low isoprenaline sensitivity. The former group had a 50% reduced in vivo lipolytic response to exercise and mental stress, despite a 50% increased plasma noradrenaline response (P < 0.01) and a 350% increased plasma adrenaline response (P < 0.02). In fat cells the lipolytic ED59 values for noradrenaline and terbutaline (BAR2 agonist) were 10 times lower (P < 0.001) in low-sensitive subjects, but the maximum lipolytic actions ofthese agents (and ofisoprenaline) were similar in both groups. The action on lipolysis of dobutamine (BAR1 agonist), forskolin (stimulating adenylate cyclase), dibuturyl cyclic AMP (activating protein kinase), clonidine (a2-adrenergic agonist), or phenyl isopropyladenosine (adenosine receptor agonist) were almost identical in high-and low-sensitivity subjects. ED5, for isoprenaline correlated with ED5, for terbutaline (r = 0.75), but not with ED5o for dobutamine. In high-sensitivity subjects the number of BAR2 was almost threefold increased (P < 0.002) and the steady-state adipocyte mRNA level for BAR2 was sixfold increased (P < 0.005).BAR2 affinity as well as BAR, number, affinity and mRNA expression were similar in both groups. In 11 cholecystectomy patients (otherwise healthy) lipolytic ED5o for 0 agonists correlated in omental and subcutaneous fat cells (r = 0.85 for isoprenaline; r = 0.95 for terbutaline). In conclusion, lipolytic resistance to catecholamines is present in vivo in apparently healthy subjects due to reduced expression of BAR2 in adipocytes. (J. Clin. Invest. 1992. 90:2175-2186

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Section: Before Aftercontrasting

confidence: 56%

Lipolytic catecholamine resistance due to decreased beta 2-adrenoceptor expression in fat cells.

Lönnqvist

Wahrenberg²,

Hellström³

et al. 1992

J. Clin. Invest.

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“…The second part of the study used yohimbine, an a2-adrenoceptor antagonist. As already mentioned, the drug clearly increased NA and Ad levels (Valet et al, 1989c) through the blockade of central and/or presynaptic x2-adrenoceptors (Goldberg & Robertson, 1983). The higher dose (0.5mg kg-') induced a marked (7 fold) increase in plasma NA values associated with similar enhancement in plasma NPY values (6.5 fold).…”

Section: Discussionmentioning

confidence: 86%

“…Thus, the aim of the present study was to investigate whether an enhancement of sympathetic tone (reflected by plasma catecholamine levels) is necessarily associated with an increase in plasma NPY levels. Two different experimental models were selected: conscious dogs subject to sinoaortic denervation, a model associated with a marked increase in sympathetic tone (Damase-Michel et al, 1987;Valet et al, 1989a, b); and conscious dogs treated with yohimbine, a drug known to activate the sympathetic nervous system (Valet et al, 1989c) through the blockade of a2-adrenoceptors located on sympathetic nerve endings (Goldberg & Robertson, 1983).…”

Section: Introductionmentioning

confidence: 99%

Changes in plasma catecholamine and neuropeptide Y levels after sympathetic activation in dogs

Poncet

Damase‐Michel

Tavernier

et al. 1992

British J Pharmacology

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1 Plasma levels of noradrenaline (NA) and neuropeptide Y (NPY) were evaluated in two experimental models associated with an increase in sympathetic tone: conscious dogs which were subject to either sinoaortic denervation or acute administration of the x2-adrenoceptor antagonist yohimbine. 2 Dogs that had undergone sinoaortic denervation exhibited a two fold increase in plasma NA without any change in NPY levels. 3 Yohimbine (0.05mgkg-1 i.v. as a bolus) produced similar effects. A higher dose of yohimbine (0.5 mg kg -i.v.) increased both plasma NA (7 fold) and NPY (6.5 fold) levels. 4 The present results indicate that changes in plasma catecholamines and NPY are not always concomitant. They suggest that the simultaneous release of NA and NPY is only observed under in vivo conditions for a marked increase in sympathetic tone.

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“…Distinctions also are found in vivo. Downregulation is greater for ␤ 2 AR than ␤ 1 AR in fat cells isolated from dogs with chronically elevated plasma catecholamines (22) and in myocardial tissue from rats infused with norepinephrine (23). The opposite, however, was found in tissue from human failing hearts (24).…”

mentioning

confidence: 99%

Resistance of the Human β1-Adrenergic Receptor to Agonist-mediated Down-regulation

Liang

Austin²,

Hoang

et al. 2003

Journal of Biological Chemistry

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Prolonged agonist stimulation results in down-regulation of most G protein-coupled receptors. When we exposed baby hamster kidney cells stably expressing the human ␤ 1 -adrenergic receptor (␤ 1 AR) to agonist over a 24-h period, we instead observed an increase of ϳ30% in both ␤ 1 AR binding activity and immune-detected receptors. In contrast, ␤ 2 AR expressed in these cells exhibited a decrease of >50%. We determined that the basal turnover rates of the two subtypes were similar (t1 ⁄2 ϳ 7 h) and that agonist stimulation increased ␤ 2 AR but not ␤ 1 AR turnover. Blocking receptor trafficking to lysosomes with bafilomycin A 1 had no effect on basal turnover of either subtype but blocked agonist-stimulated ␤ 2 AR turnover. As ␤ 1 AR mRNA levels increased in agonist-stimulated cells, ␤ 1 AR up-regulation appeared to result from increased synthesis with no change in degradation. To explore the basis for the subtype differences, we expressed chimeras in which the C termini had been exchanged. Each chimera responded to persistent agonist stimulation based on the source of its C-tail; ␤ 1 AR with a ␤ 2 AR C-tail underwent down-regulation, and ␤ 2 AR with a ␤ 1 AR C-tail underwent up-regulation. The C-tails had a corresponding effect on agonist-stimulated receptor phosphorylation and internalization with the order being ␤ 2 AR > ␤ 1 AR with ␤ 2 AR C-tail > ␤ 2 AR with a ␤ 1 AR C-tail > ␤ 1 AR. As internalization may be a prerequisite for down-regulation, we addressed this possibility by co-expressing each subtype with arrestin-2. Although ␤ 1 AR internalization was increased to that of ␤ 2 AR, down-regulation still did not occur. Instead, ␤ 1 AR accumulated inside the cells. We conclude that in unstimulated cells, both subtypes appear to be turned over by the same mechanism. Upon agonist stimulation, both subtypes are internalized, and ␤ 2 AR but not ␤ 1 AR undergoes lysosomal degradation, the fate of each subtype being regulated by determinants in its C-tail.

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Lipomobilizing effects of procaterol and yohimbine in the conscious dog: comparison of endocrinological, metabolic and cardiovascular effects

Cited by 15 publications

References 40 publications

Lipolytic catecholamine resistance due to decreased beta 2-adrenoceptor expression in fat cells.

Lipolytic catecholamine resistance due to decreased beta 2-adrenoceptor expression in fat cells.

Changes in plasma catecholamine and neuropeptide Y levels after sympathetic activation in dogs

Resistance of the Human β1-Adrenergic Receptor to Agonist-mediated Down-regulation

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