Beta2-adrenoceptors: mechanisms of action of beta2-agonists.
The human beta2-adrenoceptor is a member of the 7 transmembrane family of receptors. It is encoded by a gene on chromosome 5 and is widely distributed in the respiratory tract. Following beta2-adrenoceptor activation, intracellular signalling is mainly produced by inducing cyclic AMP. This produces airway relaxation through phosphorylation of muscle regulatory proteins and modification of cellular Ca2+concentrations. Beta2-agonists have been characterised into those which directly activate the receptor (salbutamol/terbutaline), those which are taken up into a membrane depot (formoterol) and those which interact with a receptor-specific, auxiliary binding site (salmeterol). These differences in mechanism of action are reflected in the kinetics of airway smooth muscle relaxation and bronchodilation in asthmatic patients. Beta-adrenoceptor desensitisation is associated with beta2-agonist activation and differs depending on the cell type. It is reflected in the different profiles of clinical tolerance to chronic beta2-agonist therapy. A number of polymorphisms of the beta2-receptor have been described which appear to alter the behaviour of the receptor, including the degree of downregulation and response to beta2-agonists.
Johnson
M
M
Respiratory Therapeutic Development, Glaxo SmithKline Research & Development, Uxbridge, Middlesex, UK.
D000318:Adrenergic beta-Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D002648:Child; D006801:Humans; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2