From the Guidelines
Methylxanthines do not primarily act by releasing Ca2+ from the sarcoplasmic reticulum, as this mechanism is not explicitly mentioned in the most recent and highest quality evidence available. The provided study from 1995 1 discusses the effects of methylxanthines, such as theophylline and aminophylline, in the context of chronic obstructive pulmonary disease (COPD) management, but it does not detail their mechanism of action at the level of sarcoplasmic reticulum calcium release.
Key Points
- Methylxanthines have various effects, including systemic and pulmonary vascular dilatation, increased salt and water excretion, and central nervous system stimulation 1.
- They are used for their bronchodilator effects, although these are comparable or less than those of β2-agonists or anticholinergic agents 1.
- The therapeutic effects of methylxanthines occur at blood levels >5 μg·mL-1, with side-effects increasing at levels >15 μg·mL-1 1.
Clinical Considerations
Given the information available, the primary clinical consideration for methylxanthines is their use in managing COPD and asthma, with careful monitoring of blood levels to minimize side-effects. The mechanism of action of methylxanthines involves inhibition of phosphodiesterase enzymes and antagonism of adenosine receptors, but the specific action on the sarcoplasmic reticulum is not highlighted in the provided evidence. Therefore, in clinical practice, methylxanthines should be used based on their established therapeutic effects and with careful consideration of their potential side-effects, rather than a presumed mechanism of action on calcium release from the sarcoplasmic reticulum.
From the Research
Mechanism of Action of Methylxanthines
- The mechanism of action of methylxanthines, such as theophylline, is not fully understood, but several potential targets have been suggested, including non-selective inhibition of phosphodiesterases (PDE), inhibition of phosphoinositide 3-kinase, adenosine receptor antagonism, and increased activity of certain histone deacetylases 2.
- Theophylline has been shown to have anti-inflammatory effects in asthma and chronic obstructive pulmonary disease (COPD) at lower concentrations, which may be due to inhibition of PDE4 and histone deacetylase-2 activation 3.
- Methylxanthines are also known to have anti-inflammatory and anti-oxidative properties, mediate changes in lipid homeostasis, and have neuroprotective effects, with known molecular mechanisms including adenosine receptor antagonism, phosphodiesterase inhibition, effects on the cholinergic system, wnt signaling, histone deacetylase activation, and gene regulation 4.
Release of Ca2+ from Sarcoplasmic Reticulum
- There is no direct evidence in the provided studies to suggest that methylxanthines act by releasing Ca2+ from the sarcoplasmic reticulum.
- The studies focus on the molecular mechanisms of action of methylxanthines, including inhibition of phosphodiesterases, adenosine receptor antagonism, and histone deacetylase activation, but do not mention the release of Ca2+ from the sarcoplasmic reticulum as a mechanism of action 3, 2, 5, 4.
- Further research is necessary to fully understand the mechanism of action of methylxanthines and their potential effects on Ca2+ release from the sarcoplasmic reticulum.