Rapamycin inhibits the growth and muscle-sparing effects of clenbuterol

Related Experiment Video

Updated: Jul 19, 2026

Development and Application of Rapamycin-regulated Tyrosine Phosphatases
06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

William O Kline1, Frank J Panaro, Hayung Yang

  • 1Univ. of California, Davis, Section of Neurobiology, Physiology, and Behavior, One Shields Ave., Davis, California 95616, USA.

Journal of Applied Physiology (Bethesda, Md. : 1985)
|October 28, 2006
PubMed

Insights

Clenbuterol promotes muscle growth and prevents muscle loss by activating Akt and mTOR signaling pathways. This study investigated these mechanisms in rats, revealing key molecular pathways involved in muscle hypertrophy and atrophy.

Area of Science:

  • Muscle physiology and molecular signaling.
  • Pharmacology of beta2-adrenergic agonists.

Background:

  • Beta2-adrenergic agonists like clenbuterol stimulate muscle growth and prevent atrophy via unclear mechanisms.
  • Akt and mammalian target of rapamycin (mTOR) signaling pathways are crucial for protein synthesis and cell growth.

Purpose of the Study:

  • To test if clenbuterol's muscle-growth and muscle-sparing effects are mediated by Akt and mTOR activation.
  • To elucidate the molecular mechanisms underlying clenbuterol's anabolic and anti-atrophy actions.

Main Methods:

  • Administered clenbuterol to rats to induce muscle growth and atrophy (hindlimb suspension, denervation).
  • Used rapamycin, an mTOR inhibitor, to assess mTOR's role in clenbuterol's effects.
  • Measured phosphorylation of Akt, S6K1, and 4E-BP1; assessed MuRF1 and MAFbx gene expression.

Main Results:

  • Clenbuterol increased Akt and downstream signaling (S6K1, 4E-BP1) phosphorylation.
  • Clenbuterol induced significant muscle growth (27-41%) and attenuated atrophy (10-20%) in hindlimb-suspended rats.
  • Rapamycin partially blocked clenbuterol-induced growth and completely blocked its effect in hindlimb suspension but not denervation.
  • Clenbuterol suppressed MuRF1 and MAFbx expression.

Conclusions:

  • Clenbuterol-induced muscle growth and protection against atrophy are partly mediated by Akt and mTOR activation.
  • The findings highlight the involvement of specific signaling pathways in clenbuterol's effects on muscle.
  • Rapamycin's differential effects suggest pathway involvement varies with atrophy type.

More Related Videos

A Semi-Quantitative Drug Affinity Responsive Target Stability (DARTS) assay for studying Rapamycin/mTOR interaction05:28

A Semi-Quantitative Drug Affinity Responsive Target Stability (DARTS) assay for studying Rapamycin/mTOR interaction

Published on: August 27, 2019

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin10:21

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin

Published on: September 12, 2019

Related Concept Videos

Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
Skeletal Muscle Relaxants: Adverse Effects01:21

Skeletal Muscle Relaxants: Adverse Effects

Skeletal muscle relaxants are widely used for muscle paralysis and relieving pain following any muscle injury or stiffness. However, depending on the drug type, they can have adverse effects that range from mild to severe. Usually, nondepolarizing neuromuscular blockers have minimal side effects. For example, drugs like d-tubocurarine, cisatracurium, and rocuronium cause hypotension, whereas drugs like baclofen, when stopped abruptly, can lead to the recurrence of spastic conditions.
Unlike...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Nondepolarizing (Competitive) Neuromuscular Blockers: Pharmacological Actions01:27

Nondepolarizing (Competitive) Neuromuscular Blockers: Pharmacological Actions

Nondepolarizing neuromuscular blockers prevent the membrane depolarization of muscle cells and inhibit muscle contraction. These are usually administered with anesthetics to achieve complete muscle relaxation. Upon administration, these drugs first block the small, rapidly contracting muscles of the face and hands, followed by the larger muscles of the trunk and the intercostal muscles. The diaphragm is the last muscle to be affected.
Although all competitive neuromuscular blockers are designed...
Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin01:26

Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin

Directly acting muscle relaxants like dantrolene and botulinum toxin (BoNT) have distinct mechanisms and applications. Dantrolene, a hydantoin derivative, acts on the ryanodine receptor (RYR1) in skeletal muscle cells. RYR1 are calcium channels present at the sarcoplasmic reticulum membrane. In response to excitation, they release calcium ions from the sarcoplasmic reticulum to the cytosol. Calcium promotes actin-myosin-mediated contraction of muscles.
The binding of dantrolene to the RYR1...