Function and regulation of the β3-adrenoceptor

Strosberg, A. Donny; Piétri‐Rouxel, France

doi:10.1016/s0165-6147(96)80011-3

Cited by 160 publications

(67 citation statements)

References 51 publications

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“…However, HDL-C and TG levels significantly improved in subjects without the 64Arg allele, but not in those with the 64Arg allele. β 3 -AR gene is almost exclusively expressed in adipose tissue, and subjects carrying the 64Arg allele have an impaired β 3 -AR-induced lipolysis (1)(2)(3)(4)(5)(6). β 3 -AR gene could be responsible for lipid regulation as well as lipolysis of body fat (30).…”

Section: Discussionmentioning

confidence: 99%

“…The β 3 -adrenergic receptor (β 3 -AR) gene is established as the principal mediator of thermogenesis in brown adipose tissue and lipolysis in white adipose tissue both in animals and humans (1)(2)(3)(4)(5)(6). First, Walston et al (7) found that the singlenucleotide polymorphism of the gene encoding this receptor was often observed in Pima Indians, and they suggested that the polymorphism is one of the main causes of the high prevalence of obesity in this population.…”

Section: Introductionmentioning

confidence: 99%

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Effect of β3-adrenergic receptor gene polymorphism on body weight change in middle-aged, overweight women

Lee

Kawakubo

Inoue

et al. 2006

Environ Health Prev Med

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Objectives: To examine the effects of β 3 -adrenergic receptor gene polymorphism on body weight change during a weight reduction program for middle-aged, overweight women with careful consideration of their energy intake and expenditure.Methods: Design: Intervention study of weight reduction for 12 weeks in a community setting. Subjects: Eighty overweight middle-aged women who completed the individualized lifestyle modification program. Measurements: β 3 -adrenergic receptor gene polymorphism was identified by polymerase chain reaction and consecutive restriction fragment-length polymorphism analysis. Anthropometrical parameters, lifestyle factors, blood lipid and glucose levels, physical activity level and energy intake were measured before and at the end of the program.Results: The numbers of subjects with the Trp64Trp, Trp64Arg, and Arg64Arg genotypes were 45, 30 and 5, respectively. Baseline characteristics among subjects with the Trp64Trp, Trp64Arg and Arg64Arg alleles did not differ. After 12 weeks, the subjects with the 64Arg allele had significantly smaller decrease in body weight and energy intake than those without the 64Arg allele. The change of other clinical characteristics did not differ between the two groups. After adjusting for the %change of energy intake, the %change of body weight did not differ between the two groups.Conclusion: The 64Arg allele of the β 3 -AR gene is not likely to be the factor determining the difficulty in losing body weight in Japanese middle-aged, overweight women. Lifestyle factors, such as the decrease in energy intake, might mask the effect of the 64Arg allele on body weight loss. Specific considerations for the management of energy intake would be needed to promote body weight loss for those with the 64Arg allele.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of β3-adrenergic receptor gene polymorphism on body weight change in middle-aged, overweight women

Lee

Kawakubo

Inoue

et al. 2006

Environ Health Prev Med

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“…In the present study, the properties of the b 3 -adrenoceptor increasing BAT temperature (for review, see Arch & Kaumann, 1993;Galitzky et al, 1995;Strosberg & Pietri-Rouxel, 1996) and the atypical b-adrenoceptor increasing heart rate were directly compared in pithed and vagotomized rats. In our experiments, the level of basal blood pressure was increased by [Lys 8 ]-vasopressin in order to allow comparisons with our previous study (Malinowska & Schlicker, 1996); furthermore, a high level of blood pressure proved favourable for measuring thermogenesis in BAT.…”

Section: Discussionmentioning

confidence: 99%

Further evidence for differences between cardiac atypical β‐adrenoceptors and brown adipose tissue β3‐adrenoceptors in the pithed rat

Malinowska¹,

Schlicker²

1997

British J Pharmacology

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1 We have previously shown (Malinowska & Schlicker, 1996) that the atypical b-adrenoceptor involved in the positive chronotropic e ect of the so-called non-conventional partial b-adrenoceptor agonists CGP 12177 and cyanopindolol in the pithed rat possesses properties markedly di erent from those observed for b 3 -adrenoceptors in the literature. In the present study, we have directly compared the pharmacological properties of the atypical cardiostimulant b-adrenoceptor and of the b 3 -adrenoceptor mediating the thermogenic response in the brown adipose tissue in pithed and vagotomized rats. 2 Heart rate was dose-dependently increased by CGP 12177 and cyanopindolol by maximally 150 and 100 beats min 71 , yielding pED 50 values of 8.0 and 7.3, respectively (pED 50 , 7log 10 of the dose in mol kg 71 body weight i.v. causing the half-maximum e ect), but not a ected by the selective b 3 -adrenoceptor agonist CL 316243 (pED 50 46.0). 3 CGP 12177, cyanopindolol and CL 316243 increased temperature in the brown adipose tissue by maximally 18C (pED 50 values 7.4, 6.3 and 8.6, respectively). 4 The b 1 -adrenoceptor antagonist CGP 20712 10 mmol kg 71 , attenuated the cardiostimulatory e ect of CGP 12177 and, at a still higher dose (30 mmol kg 71 ), also antagonized its thermogenic e ect. The 7log 10 values of the doses causing a two fold shift of the dose-response curves (DRCs) of CGP 12177 to the right were 6.1 and 5.2, respectively, and were much lower than the corresponding value for the antagonism of CGP 20712 against the b 1 -adrenoceptor-mediated positive chronotropic e ect which was 8.6. 5 The cardiostimulant and the thermogenic e ect of CGP 12177 were not a ected by the b 2 -adrenoceptor antagonist ICI 118551 10 mmol kg 71 . 6 The b 3 -adrenoceptor antagonist SR 59230A (which, by itself, caused a b 1 -adrenoceptor-mediated increase in heart rate and, for this reason, was studied after administration of a low dose of CGP 20712) attenuated the cardiostimulant and the thermogenic e ect of CGP 12177 to a similar extent. The 7log 10 values of the doses causing two fold rightward shifts of the DRCs of CGP 12177 were 5.9 and 5.7, respectively. 7 The non-selective b-adrenoceptor antagonist bupranolol diminished the cardiostimulant and thermogenic response to a very similar extent. The 7log 10 values causing two fold rightward shifts of the DRCs of CGP 12177 were 5.6 and 5.7, respectively, and were much lower than the corresponding values for the antagonism of bupranolol against the b 1 -adrenoceptor-mediated positive chronotropic e ect and the b 2 -adrenoceptor-mediated decrease in diastolic blood pressure which were 7.6 and 8.3, respectively. 8 The rank order of agonistic potencies for the cardiostimulant e ect (CGP 121774cyanopindolol 4 CL 316243) di ers from that for the thermogenic response in the brown adipose tissue (CL 3162434CGP 121774cyanopindolol); furthermore, there is a di erence with respect to the rank orders of antagonistic potencies for cardiostimulation (CGP 207125SR 59230A5bupranolol4ICI 118551) and thermo...

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“…For example, the b 1 and b 2 adrenoceptors are known to participate in stress-related behavioral changes (Gorman and Dunn, 1993;Gurguis et al, 1999;Cecchi et al, 2002) and to mediate the effects of antidepressant treatment (Hancock and Marsh, 1985;Stahl et al, 1987;Manier et al, 1989;Holoubek et al, 2004). Among the b-adrenergic receptor subtypes, little is known about the central role of the G Sprotein-coupled b 3 subtype (Strosberg and Pietri-Rouxel, 1996), which, albeit mainly present in peripheral tissues, has been found in small quantities in the human and rat brain. Initially, the existence of the b 3 adrenoceptor in the brain was questioned, as classical binding studies had failed to detect its presence in central tissues.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the availability of the selective b 3 -adrenoceptor agonist SR58611A (amibegron) has opened new avenues for exploring the possible involvement of the b 3 adrenoceptor in the modulation of stress-related disorders Manara and Bianchetti, 1990). SR58611A, which is chemically related to the phenylaminotetralines family, displays high efficacy and potency at the rat and human b 3 receptor, 280-and 140-fold selectivity for rat b 3 as compared with b 1 and b 2 receptors, and is inactive at a number of other central targets involved in the regulation of stress-related disorders Simiand et al, 1992;Strosberg and Pietri-Rouxel, 1996). In a previous report, Simiand et al (1992) have shown that SR58611A behaved like an antidepressant in mechanistic models considered to be predictive of clinical antidepressant activity (ie, antagonism of drug-induced hypothermia, toxicity produced by yohimbine) and in the learned helplessness test in rats.…”

Section: Introductionmentioning

confidence: 99%

Stimulation of the β3-Adrenoceptor as a Novel Treatment Strategy for Anxiety and Depressive Disorders

Stemmelin

Cohen

Terranova

et al. 2007

Neuropsychopharmacol

109

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The characterization of the first selective orally active and brain-penetrant b 3 -adrenoceptor agonist, SR58611A (amibegron), has opened new possibilities for exploring the involvement of this receptor in stress-related disorders. By using a battery of tests measuring a wide range of anxiety-related behaviors in rodents, including the mouse defense test battery, the elevated plus-maze, social interaction, stressinduced hyperthermia, four-plate, and punished drinking tests, we demonstrated for the first time that the stimulation of the b 3 receptor by SR58611A resulted in robust anxiolytic-like effects, with minimal active doses ranging from 0.3 to 10 mg/kg p.o., depending on the procedure. These effects paralleled those obtained with the prototypical benzodiazepine anxiolytic diazepam or chlordiazepoxide.Moreover, when SR58611A was tested in acute or chronic models of depression in rodents, such as the forced-swimming and the chronic mild stress tests, it produced antidepressant-like effects, which were comparable in terms of the magnitude of the effects to those of the antidepressant fluoxetine or imipramine. Supporting these behavioral data, SR58611A modified spontaneous sleep parameters in a manner comparable to that observed with fluoxetine. Importantly, SR58611A was devoid of side effects related to cognition (as shown in the Morris water maze and object recognition tasks), motor activity (in the rotarod), alcohol interaction, or physical dependence. Antagonism studies using pharmacological tools targeting a variety of neurotransmitters involved in anxiety and depression and the use of mice lacking the b 3 adrenoceptor suggested that these effects of SR58611A are mediated by b 3 adrenoceptors. Taken as a whole, these findings indicate that the pharmacological stimulation of b 3 adrenoceptors may represent an innovative approach for the treatment of anxiety and depressive disorders.

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Function and regulation of the β3-adrenoceptor

Cited by 160 publications

References 51 publications

Effect of β3-adrenergic receptor gene polymorphism on body weight change in middle-aged, overweight women

Effect of β3-adrenergic receptor gene polymorphism on body weight change in middle-aged, overweight women

Further evidence for differences between cardiac atypical β‐adrenoceptors and brown adipose tissue β3‐adrenoceptors in the pithed rat

Stimulation of the β3-Adrenoceptor as a Novel Treatment Strategy for Anxiety and Depressive Disorders

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