b2 adrenoceptors are mainly associated with causing relaxation of smooth muscle in a variety of tissues (see diagram below). The b2 subtype has a high affinity for the endogenous agonist adrenaline. Synthetic b2 agonists include terbutaline, salbutamol, salmeterol and zinterol, all of which have proved therapeutically useful in the treatment of asthma. Selective b2 antagonist have also been identified these include butoxamine and ICI118 551.
Diagram adapted from Pharmacology (4th edition) Rang Dale and Ritter
The location of b2 adrenoceptors can be identified using the radiolabelled ligand [3H] dihydroalprenolol or [125I] iodopindolol and its analogues.
b2 adrenoceptors have been cloned and expressed in a variety of species. Cloning was first achieved by screening hamster genomic libraries with oligonucleotides complimentary to peptide fragments of purified hamster lung b2 adrenoceptors. This yielded a clone that when expressed had functional and radioligand-binding characteristics consistent with those of the b2 adrenoceptors. Furthermore there appears to be only minor species differences between these clones, with approximately 87 to 93% overall amino acid identity.
Catecholamines acting on b2 adrenoceptors mediate a number of tissue responses. Bronchial smooth muscle is strongly dilated by activation of b2 receptors. Uterine smooth muscle responds in a similar way and b2 agonist are frequently used to delay premature labour. Skeletal muscle is also affected by adrenaline acting on b2 receptors though the effect is far less dramatic than that on the heart. The twitch tension of fast contracting fibres (white muscle) is increased by adrenaline, particularly if the muscle is fatigued, whereas the twitch of slow (red) muscle is reduced.
In man adrenaline and other b2 agonists cause a marked tremor, this is demonstrated in the shakiness that accompanies fear and excitement or the excessive use of b2 agonists (treatment of asthma being an example of this). This tremor possibly results from an increase in muscle spindle discharge coupled with an effect on the contraction kinetics of the fibres, these effects to combine to produce instability in the reflex control of muscle length.
b2 agonists also cause long term changes in expression of the sarcoplasmic reticulum proteins that control contraction kinetics and thereby increase the rate and force of contraction of skeletal muscle. Clenbuterol is a b2 agonist, which acts in this way and has been used illegally by "sportsmen" to enhance performance.
Histamine release is also inhibited by catecholamines acting apparently at b2 receptors on mast cells and the release of glucose from the liver is also controlled by b2 receptors leading to glycogenolysis.
b2 adrenoceptors are also positively coupled to the membrane bound enzyme adenylate cyclase via activation of Gs G-protein. b2 adrenoceptor activation causes relaxation of smooth muscle through the activation of adenylate cyclase. Stimulation of adenylate cyclase produces alterations in cellular activity by increasing levels of cAMP. The resulting increased levels of cAMP activate protein kinase A, which phosphorylates and inactivates myocin light chain kinase (MLCK), the contractile machinery of smooth muscle.