Ball-and-stick model of R-albuterol (top) and S-albuterol (bottom). "RS-salbutamol-from-xtal-3D-balls" by Ben Mills - Own work. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:RS-salbutamol-from-xtal-3D-balls.png#/media/File:RS-salbutamol-from-xtal-3D-balls.png

Albuterol

Albuterol is an agonist of the [beta]-adrenergic receptor (β2-AR). It is commonly available in two forms, R-albuterol (or levalbuterol) and S-albuterol¹. Levalbuterol is often regarded as the active form of this molecule, as S-albuterol as been found to remain in circulation for up to twelve times longer than its other isomer¹.

Albuterol and Respiration

This class of drug elicits bronchodilation through the recruitment of sodium/potassium ATPases in the alveoli of animal lungs via changes in calcium concentrations². A recent study has found that this is associated with calcium release-activated calcium channels linked to stromal interaction molecule 1 (STIM1)². A rat model of acute respiratory distress syndrome (ARDS) found that the genes for sodium/potassium ATPase-α were significantly increased in response to intratracheal and intravenous albuterol, but only if alveolar ion channel and aquaporin gene expression were elevated beforehand (i.e. by experimental ARDS induction)³.

Albuterol is often used as a standard when assessing the binding (and other) properties of novel β2-AR agonists⁴. It was also recently used to validate the bronchoconstrictive properties of insulin in a study using guinea pigs⁵. Albuterol has also been found to potentiate concurrently-available corticosteroids and modulate inflammatory responses when inhaled¹.

Albuterol and Cardiovascular Research

Albuterol has been proposed as a preventative against hypoxia (oxygen deprivation) in anesthetized animals. However, it is also linked to increased risks of cardiac complications (e.g. changes in heart rate) due to its effects on β2-ARs outside the lungs⁶. An electrophysiological study using mice with experimentally-induced heart failure found that this intervention resulted in significantly decreased bronchial tissue responses to albuterol⁷. This was most probably due to significant decreases in β2-AR expression following heart failure⁷.

Albuterol and Body Composition(?)

Albuterol may also have positive effects on fat accumulation and metabolism. A group of researchers have claimed that doses of albuterol, caffeine or both increased lipid breakdown in cultured lipocytes⁸. They also reported a long-term trend of increased metabolic rates in rats, although increases in lean body mass and reductions in fat mass in response to the combination of caffeine and albuterol was greater compared to those associated with albuterol alone⁸.

References:

1. Ameredes BT, Calhoun WJ. Levalbuterol versus albuterol. Curr Allergy Asthma Rep. 2009;9(5):401-409.

2. Keller MJ, Lecuona E, Prakriya M, et al. Calcium release-activated calcium (CRAC) channels mediate the beta(2)-adrenergic regulation of Na,K-ATPase. FEBS Lett. 2014;588(24):4686-4693.

3. Uhlig C, Silva PL, Ornellas D, et al. The effects of salbutamol on epithelial ion channels depend on the etiology of acute respiratory distress syndrome but not the route of administration. Respir Res. 2014;15:56.

4. Baker JG, Proudman RG, Hill SJ. Salmeterol's extreme beta2 selectivity is due to residues in both extracellular loops and transmembrane domains. Mol Pharmacol. 2015;87(1):103-120.

5. Sharif M, Khan BT, Ajmal K, Anwar MA. Acute effect of insulin on guinea pig airways and its amelioration by pre-treatment with salbutamol. J Pak Med Assoc. 2014;64(8):932-935.

6. Casoni D, Spadavecchia C, Adami C. Cardiovascular changes after administration of aerosolized salbutamol in horses: five cases. Acta Veterinaria Scandinavica. 2014;56(1):49-49.

7. Rinaldi B, Capuano A, Gritti G, et al. Effects of chronic administration of beta-blockers on airway responsiveness in a murine model of heart failure. Pulm Pharmacol Ther. 2014;28(2):109-113.

8. Liu AG, Arceneaux KP, 3rd, Chu JT, et al. The effect of caffeine and albuterol on body composition and metabolic rate. Obesity (Silver Spring). 2015.