The human near‐term myometrial β3‐adrenoceptor but not the β2‐adrenoceptor is resistant to desensitisation after sustained agonist stimulation

Rouget, C; Breuiller‐Fouché, M; Mercier, F J; Leroy, M J; Loustalot, C; Naline, E; Frydman, R; Croci, T; Morcillo, E J; Advenier, C; Bardou, M

doi:10.1038/sj.bjp.0705616

Cited by 31Receptor Mechanisms and SignalingPhosphodiesterase function and regulationNeuropeptides and Animal Physiology

The human near‐term myometrial β3‐adrenoceptor but not the β2‐adrenoceptor is resistant to desensitisation after sustained agonist stimulation

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Rouget, C, Breuiller‐Fouché, M, Mercier, F J, Leroy, M J, Loustalot, C, Naline, E, Frydman, R, Croci, T +3 more·2004·British Journal of Pharmacology

DOI 10.1038/sj.bjp.0705616PMC PMC1574252

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Abstract

1. In order to compare the beta(2)- and beta(3)-adrenoceptor (beta-AR) desensitisation process in human near-term myometrium, we examined the influence of a pretreatment of myometrial strips with either a beta(2)- or a beta(3)-AR agonist (salbutamol or SR 59119A, respectively, both at 10 microm, for 5 and 15 h) on the relaxation and the cyclic adenosine monophosphate (cAMP) production induced by these agonists. 2. To assess some of the mechanisms potentially implicated in the beta-AR desensitisation process, we studied the influence of such treatment on the number of beta(2)- and beta(3)-AR binding sites, the beta(2)- and beta(3)-AR transcripts expression and the phosphodiesterase 4 (PDE4) activity. 3. Salbutamol, but not SR 59119A, concentration-response curve (CRC) was shifted by a 15 h salbutamol preincubation, with a significant difference in -log EC(20) values (6.31+/-0.13 vs 5.58+/-0.24, for control and 15 h salbutamol pretreatment, respectively, P<0.05). Neither salbutamol nor SR 59119A CRCs were modified after a 15 h preincubation with SR 59119A. 4. A 15 h exposure of myometrial strips to salbutamol significantly reduced the salbutamol-induced (0.60+/-0.26 vs 1.54+/-0.24 pmol mg(-1) protein, P<0.05), but not the SR 59119A-induced, cAMP production. No decrease in cAMP production was observed after a 15 h SR 59119A exposure. 5. A 15 h salbutamol exposure of myometrial strips significantly reduced the beta(2)- but not the beta(3)-AR binding site density, whereas no decrease in the number of beta(2)- and beta(3)-AR binding sites was observed after a 15 h SR 59119A treatment. 6. Neither PDE4 activity nor the beta(2)- and beta(3)-AR mRNA expression levels were affected by salbutamol or SR 59119A treatments. 7. Our results indicate that beta(3)-AR, but not beta(2)-AR, are resistant to the agonist-induced desensitisation. In our model, beta(2)-AR desensitisation is mediated by a decreased number of beta(2)-AR that was not explained by transcriptional regulation of the receptor.

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Unlike ADRB1 or ADRB2, ADRB3 has been shown to be less easily desensitized.
“Unlike ADRB1 or ADRB2, ADRB3 has been shown to be less easily desensitized (Rouget et al., 2004), thus providing more durable responsiveness to adrenergic outflow.”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Rouget et al., 2004

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Authors: Rouget, C., Breuiller‐Fouché, M., Mercier, F. J., Leroy, M. J., Loustalot, C., Naline, E., Frydman, R., Croci, T., Morcillo, E. J., Advenier, C., & Bardou, M.
Affiliations: Inserm (FR)
Hôpital Antoine-Béclère (FR)
Sanofi (Italy) (IT)
Universitat de València (ES)
Université de Bourgogne (FR)
Corresponding author: Rouget, C
Bardou, M
ORCID: Mercier, F J
Morcillo, E J
Bardou, M
Venue: British Journal of Pharmacology
Publisher: Wiley
Published: 2004-03
Volume: 141
Issue: 5
Pages: 831-841
ISSN: 0007-1188 (ISSN-L)
1476-5381
DOI: 10.1038/sj.bjp.0705616
PMC: PMC1574252
OpenAlex: W1992855284
Cited by: 31
References: 69
Citations by year: 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2015: 1 · 2014: 1 · 2013: 1
FWCI: 1.18
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1796 d)
Locations: British Journal of Pharmacology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: beta3-adrenergic receptor, beta2-adrenergic receptor, receptor desensitization, salbutamol, cyclic AMP, phosphodiesterase 4, myometrial relaxation, preterm labour, uterine contractility
MeSH terms: Adrenergic beta-Agonists, Albuterol, Analysis of Variance, Dose-Response Relationship, Drug, Female, Humans, Myometrium, Pregnancy, Protein Binding, Receptors, Adrenergic, beta-2, Receptors, Adrenergic, beta-3, Adrenergic beta-2 Receptor Agonists, Adrenergic beta-3 Receptor Agonists, In Vitro Techniques

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The human near‐term myometrial β3‐adrenoceptor but not the β2‐adrenoceptor is resistant to desensitisation after sustained agonist stimulation

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