Beta2-adrenoceptors: mechanisms of action of beta2-agonists

Paediatr Respir Rev. 2001 Mar;2(1):57-62. doi: 10.1053/prrv.2000.0102.

Abstract

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.

MeSH terms

  • Adrenergic beta-Agonists / pharmacokinetics
  • Adrenergic beta-Agonists / pharmacology*
  • Child
  • Humans
  • Polymorphism, Genetic
  • Receptors, Adrenergic, beta-2 / drug effects
  • Receptors, Adrenergic, beta-2 / genetics
  • Receptors, Adrenergic, beta-2 / physiology*

Substances

  • Adrenergic beta-Agonists
  • Receptors, Adrenergic, beta-2