Combinatory in vitro effects of the β2-agonists salbutamol and formoterol in skeletal muscle cells
Abstract
β2-agonists are used for the treatment of bronchoconstriction, but also abused in doping. Beside an ergogenic activity β2-agonists may have also anabolic activity. Therefore, we investigated the anabolic activity and associated molecular mechanisms of Salbutamol (SAL) and Formoterol (FOR) alone, as well as in combination in C2C12 myotubes. In differentiated C2C12 cells, dose-dependent effects of SAL and FOR (alone/in combination) on myotube diameter, myosin heavy chain (MHC) protein expression and the mRNA expression of genes involved in hypertrophy were analyzed. β2-adrenoceptor 2 (ADRB2), androgen receptor (AR) and estrogen receptor (ER) inhibitors, as well as dexamethasone (Dexa) were co-incubated with the β2-agonists and myotube diameter was determined. SAL and FOR treatment significantly induced hypertrophy and increased MHC expression and the mRNA expression of Igf1, mTOR, PIk3r1 and AMpKa2. In contrast to an ER inhibitor, the ADRB2 and AR inhibitors, as well as Dexa antagonized FOR and SAL induced hypertrophy. Combined treatment with SAL and FOR resulted in significant additive effects on myotube diameter and MHC expression. Future clinical studies are needed to prove this effect in humans and to evaluate this finding with respect to antidoping regulations.
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The C2C12 cell line-based assay is well-established and has been used in numerous other studies.
“a well-established C2C12 cell line-based assay, that has been used in numerous other studies [7,21,66–68].”
From How reliable is the labeling of a commercial phytosteroid product? A 12-week randomized double-blind training study (2025) · cites this paper as [67]
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- Authors
- Piribauer, M., Jiang, L., Kostov, T., Parr, M., Steidel, S., Bizjak, D. A., Steinacker, J. M., & Diel, P.
- Affiliations
- German Sport University Cologne (DE)
- Freie Universität Berlin (DE)
- University Hospital Ulm (DE)
- Corresponding author
- Diel, P.
- Venue
- Toxicology Letters
- Publisher
- Elsevier BV
- Published
- 2023-04
- Volume
- 378
- Pages
- 10-18
- ISSN
- 0378-4274 (ISSN-L)
- OpenAlex
- W4321438460
- Cited by
- 10
- References
- 44
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 6
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Toxicology Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- World Anti-Doping Agency (15C13MZ)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Pharmacological Effects and Assays
- Social Sciences › Sociology and Political Science › Doping in Sports
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- beta2-adrenergic agonists, salbutamol, formoterol, skeletal muscle hypertrophy, anabolic activity, doping, C2C12 myotubes, myosin heavy chain, ADRB2, androgen receptor, estrogen receptor, dexamethasone, insulin-like growth factor I, mTOR, PI3K/Akt signaling, AMPK, additive drug effects
- MeSH terms
- Formoterol Fumarate, Adrenergic beta-Agonists, Albuterol, Humans, Hypertrophy, Penicillins, RNA, Messenger, Muscle, Skeletal, Muscle Fibers, Skeletal
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