The rush to adrenaline: drugs in sport acting on the β‐adrenergic system

Abstract

Athletes attempt to improve performance with drugs that act on the b-adrenergic system directly or indirectly. Of three b-adrenoceptor (AR) subtypes, the b 2 -AR is the main target in sport; they have bronchodilator and anabolic actions and enhance anti-inflammatory actions of corticosteroids. Although demonstrable in animal experiments and humans, there is little evidence that these properties can significantly improve performance in trained athletes. Their actions may also be compromised by receptor desensitization and by common, naturally occurring receptor mutations (polymorphisms) that can influence receptor signalling and desensitization properties in individuals. Indirectly acting agents affect release and reuptake of noradrenaline and adrenaline, thereby influencing all AR subtypes including the three b-ARs. These agents can have potent psychostimulant effects that provide an illusion of better performance that does not usually translate into improvement in practice. Amphetamines and cocaine also have considerable potential for cardiac damage. b-AR antagonists (b-blockers) are used in sports that require steadiness and accuracy, such as archery and shooting, where their ability to reduce heart rate and muscle tremor may improve performance. They have a deleterious effect in endurance sports because they reduce physical performance and maximum exercise load. Recent studies have identified that many b-AR antagonists not only block the actions of agonists but also activate other (mitogen-activated PK) signalling pathways influencing cell growth and fate. The concept that many compounds previously regarded as 'blockers' may express their own spectrum of pharmacological properties has potentially far-reaching consequences for the use of drugs both therapeutically and illicitly. Keywords: b-adrenoceptor; b-blocker; polymorphism; ergogenic; sympathomimetic; clenbuterol; salbutamol; ephedrine Abbreviations: AR, adrenoceptor; Gs, stimulatory G-protein; Erk1/2, extracellular-signal regulated kinase; TNFa, tumour necrosis factor a There has been considerable interest expressed in the use of drugs by athletes to improve performance. As the physiological secretion of adrenaline into the bloodstream in response to stress, fright or physical exercise undeniably affects performance, it is not surprising that a number of categories of drugs that are used by some athletes to alter performance have their effects on the adrenergic system. The main categories of drugs acting on the adrenergic system that have been used acutely include stimulants such as cocaine, amphetamines and ephedrine (see Docherty, 2008), and blockers such as the b-AR antagonists (The World Anti-Doping Code-The 2008 Prohibited List International Standard). Most of the desired effects are produced by these drugs acting directly or indirectly on b-ARs both in the brain and in peripheral tissues. More recently, b-AR agonists have been used as anabolic agents to increase body weight and build muscle strength. This review will examine not only the characteri...

Enhanced Dendritic Cell Antigen Uptake via α2 Adrenoceptor-Mediated PI3K Activation Following Brief Exposure to Noradrenaline

“…The ARs are G protein-coupled receptors (GPCRs) that are composed of a 1 , a 2 , and b ARs that are coupled with Gq, Gi, and Gs proteins, respectively (14)(15)(16). Although the effect of NA on cytokine production by DCs has been established (10)(11)(12), the influence of this catecholamine on other DC functions is not well documented.…”

“…NA-induced alteration of cytokine production seems to be mainly mediated via b ARs. The b AR pathway elevates intracellular cAMP level via Gs protein and, thereby, activates PKA (16). PKA activation seems to induce inhibition of IL-12 production and enhancement of IL-10 production in DCs (13).…”

“…The b ARs are coupled with G proteins responsible for intracellular cAMP elevation and subsequent PKA activation (16). We next examined the involvement of PKA in NA-mediated alteration of cytokine production by DCs using a PKA-specific inhibitor H89 (Fig.…”

“…It seems that NA-mediated alteration of cytokine balance is involved, at least in part, in immune suppression upon chronic stress. The AR family is composed of a 1 (a 1A , a 1B , and a 1D ), a 2 (a 2A , a 2B , and a 2C ), and b (b 1 , b 2 , and b 3 ) receptors, coupled with guanine nucleotide-binding protein (G protein) (14)(15)(16). The effect of NA on cytokine production seems to be mainly mediated via b ARs coupled with Gs proteins responsible for the elevation of intracellular cAMP levels and the activation of protein kinase A (PKA) (10)(11)(12).…”

Effects of inhaled bronchodilators on lung function and cycling performance in female athletes with and without exercise-induced bronchoconstriction

“…In the lung, IBAs act as bronchodilators by inducing smooth muscle relaxation in the cells surrounding the airways. 2 In the heart and * Corresponding author.…”