Effects of the β3-adrenoceptor (Adrb3) agonist SR58611A (amibegron) on serotonergic and noradrenergic transmission in the rodent: Relevance to its antidepressant/anxiolytic-like profile

Claustre, Y.; Leonetti, M.; Santucci, Vincent; Bougault, I.; Desvignes, Christophe; Rouquier, L.; Aubin, N.; Keane, P.E.; Busch, Stefan; Chen, Y.; Palejwala, Vaseem A.; Tocci, Michael J.; Yamdagni, Preeti; Didier, Michel; Avenet, Patrick; Fur, G. Le; Oury-Donat, Florence; Scatton, B.; Steinberg, R.

doi:10.1016/j.neuroscience.2008.07.011

Cited by 52 publications

(36 citation statements)

References 44 publications

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“…β 3 -ARs are also expressed in the hypothalamus 38 ; thus, the possibility exists that the antidiuretic effect of BRL37344 may involve hypothalamic regulation of AVP release. Our results in AVPR2-null mice 31 seem to exclude this possibility.…”

Section: Discussionmentioning

confidence: 99%

β3 adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function

Procino

Carmosino

Milano

et al. 2016

Kidney International

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To date, the study of the sympathetic regulation of renal function has been restricted to the important contribution of β1- and β2-adrenergic receptors (ARs). Here we investigate the expression and the possible physiologic role of β3-adrenergic receptor (β3-AR) in mouse kidney. The β3-AR is expressed in most of the nephron segments that also express the type 2 vasopressin receptor (AVPR2), including the thick ascending limb and the cortical and outer medullary collecting duct. Ex vivo experiments in mouse kidney tubules showed that β3-AR stimulation with the selective agonist BRL37344 increased intracellular cAMP levels and promoted 2 key processes in the urine concentrating mechanism. These are accumulation of the water channel aquaporin 2 at the apical plasma membrane in the collecting duct and activation of the Na-K-2Cl symporter in the thick ascending limb. Both effects were prevented by the β3-AR antagonist L748,337 or by the protein kinase A inhibitor H89. Interestingly, genetic inactivation of β3-AR in mice was associated with significantly increased urine excretion of water, sodium, potassium, and chloride. Stimulation of β3-AR significantly reduced urine excretion of water and the same electrolytes. Moreover, BRL37344 promoted a potent antidiuretic effect in AVPR2-null mice. Thus, our findings are of potential physiologic importance as they uncover the antidiuretic effect of β3-AR stimulation in the kidney. Hence, β3-AR agonism might be useful to bypass AVPR2-inactivating mutations.

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Section: Discussionmentioning

confidence: 99%

β3 adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function

Procino

Carmosino

Milano

et al. 2016

Kidney International

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“…β 3 ARs are located on primary afferent nociceptors, 52 adipocytes 48 and immune cells 45,46 in the periphery and noradrenergic neurons in brain. 53 Thus, we hypothesized that peripheral, spinal, and/or central β 2 - and β 3 ARs contribute to persistent COMT-dependent pain.…”

Section: Introductionmentioning

confidence: 99%

Persistent Catechol-O-methyltransferase–dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors

2016

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Background Patients with chronic pain disorders exhibit increased levels of catecholamines alongside diminished activity of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. The authors found that acute pharmacologic inhibition of COMT in rodents produces hypersensitivity to mechanical and thermal stimuli via β-adrenergic receptor (βAR) activation. The contribution of distinct βAR populations to the development of persistent pain linked to abnormalities in catecholamine signaling requires further investigation. Methods Here, the authors sought to determine the contribution of peripheral, spinal, and supraspinal βARs to persistent COMT-dependent pain. They implanted osmotic pumps to deliver the COMT inhibitor OR486 (Tocris, USA) for 2 weeks. Behavioral responses to mechanical and thermal stimuli were evaluated before and every other day after pump implantation. The site of action was evaluated in adrenalectomized rats receiving sustained OR486 or in intact rats receiving sustained βAR antagonists peripherally, spinally, or supraspinally alongside OR486. Results The authors found that male (N = 6) and female (N = 6) rats receiving sustained OR486 exhibited decreased paw withdrawal thresholds (control 5.74 ± 0.24 vs. OR486 1.54 ± 0.08, mean ± SEM) and increased paw withdrawal frequency to mechanical stimuli (control 4.80 ± 0.22 vs. OR486 8.10 ± 0.13) and decreased paw withdrawal latency to thermal heat (control 9.69 ± 0.23 vs. OR486 5.91 ± 0.11). In contrast, adrenalectomized rats (N = 12) failed to develop OR486-induced hypersensitivity. Furthermore, peripheral (N = 9), but not spinal (N = 4) or supraspinal (N = 4), administration of the nonselective βAR antagonist propranolol, the β2AR antagonist ICI-118,511, or the β3AR antagonist SR59230A blocked the development of OR486-induced hypersensitivity. Conclusions Peripheral adrenergic input is necessary for the development of persistent COMT-dependent pain, and peripherally-acting βAR antagonists may benefit chronic pain patients.

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“…Amibegron or SR58611A, which is the first selective β3-ARs agonist described with antidepressant (Tanyeri et al, 2013b) and anxiolytic (Tanyeri et al, 2013a) properties in rodents, has been used in studies that have raised the importance of β3-AR as a target for treatment of depression (Claustre et al, 2008;Tanyeri et al, 2013b). Herein, two important facts have to be mentioned; first, β3 adrenergic chronic signaling during social stress represents an adaptive response (Chuang et al, 2010) and secondly, the study about the antidepressant-like effects of the amibegron, was coherent with the hypothesis that β3-AR might constitute a target for the pharmacotherapy of stress-related disorders (Tamburella et al, 2010).…”

Section: Beta 3 Adrenergic Receptorsmentioning

confidence: 99%

“…In fact, the activation of the β3-AR has been suggested to increase brain serotonin synthesis (Consoli et al, 2007) whereas amibegron anxiolytic-and antidepressant-like activities might be mediated, at least in part, via the increase of brain serotonergic and noradrenergic neurotransmissions (Claustre et al, 2008). Finally, it was proposed that neuronal production can be increased via the activation of both neurogenic precursors and stem cells through β3-ARs and points out a new therapeutic target for novel antidepressants (Jhaveri et al, 2010).…”

Section: Beta 3 Adrenergic Receptorsmentioning

confidence: 99%

Elements toward novel therapeutic targeting of the adrenergic system

Ghanemi

2015

Neuropeptides

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Effects of the β3-adrenoceptor (Adrb3) agonist SR58611A (amibegron) on serotonergic and noradrenergic transmission in the rodent: Relevance to its antidepressant/anxiolytic-like profile

Cited by 52 publications

References 44 publications

β3 adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function

β3 adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function

Persistent Catechol-O-methyltransferase–dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors

Elements toward novel therapeutic targeting of the adrenergic system

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