Beta-2 adrenergic receptor

• OMIM: 109690
• UniProt: P07550
• MGI: 87938

The β2 -adrenoceptor, often called β2 -adrenergic receptor, a cell membrane - bound protein belonging to the family of G- protein-coupled receptors, beta- adrenergic receptors. It is next to the Rhodopsin the best-studied protein of this family. The β2 - adrenoceptor is activated by the hormone adrenaline, and is one for which the smooth muscle relaxing, glucose release and muskelanabole effect responsible.

Occurrence

The β2 - adrenergic receptor can be detected in vertebrates and comes with the representatives of the class of mammals ubiquitously in many representatives of the subphylum. The evolutionary origin of the β2 -adrenoceptors and the cleavage of β -adrenoceptors to other by gene duplication can be extrapolated to the late Neoproterozoic or early Paleozoic.

In the human organism of the β2 - adrenergic receptor is common and can be found in particular in the cell membranes of smooth muscle cells, nerve cells, and fat cells. In addition to the dominant β1 - adrenoceptor he comes in large quantity also in the heart.

Biochemistry

Genetics

The β2 - adrenergic receptor is encoded by the intronless ADRB2 gene. The ADRB2 gene of humans is located on chromosome 5 in the 5q31 - q32 locus. Polymorphisms and point mutations of the gene are associated among other things with asthma, obesity and cardiovascular disease.

Structure

The β2 - adrenoceptor is one of the few G- protein -coupled receptors, whose structure was elucidated by means of X-ray crystallography. For him, are structural data for both the active and the inactive state, which were obtained after stabilization by fusion with the relatively easy to crystallize lysozyme of T4 phage ( T4 lysozyme ) or by complexation with the help of Fab antibody fragments or single domain antibodies. As a characteristic motif of the β2 - adrenoceptor, like all other known G protein-coupled receptors that span the cell membrane seven α - helices. As with rhodopsin itself an eighth α -helix connects to the intracellular end of transmembrane helix 7. In addition, the β2 - adrenoceptor has another α -helical structural motif, which is located extracellularly between the Tansmembranhelices 4 and 5. A ligand binding site, to which the endogenous ligand and adrenaline numerous drugs bind, is located on the outer side of the cell transmembrane helices. The cell- inner loops, however, bear binding sites for the effector proteins involved in signal transduction, in particular G- proteins.

Receptor activation

The β2 - adrenergic receptor is activated by binding of its endogenous ligands epinephrine. To a lesser extent, i.e. with an approximately 30-fold lower affinity, binds and activates the mainly acting as a neurotransmitter noradrenaline this receptor. By the binding of these ligands, the active state of the receptor to stabilize. In this state, the receptor is able to activate G proteins intracellularly bound and thus to start a signal transduction cascade. About the β2 - adrenoceptor Gs proteins are preferentially activated, which in turn activate adenylyl cyclases and increase intracellular cAMP levels. But G- proteins of the Gi family / o may couple to this receptor. Additional interaction partners of the β2 - adrenergic receptor, β -arrestin, for example, and G- protein -coupled receptor kinases.

Function

The β2 - adrenergic receptor is primarily responsible for the relaxation of smooth muscle by adrenaline. Thus, an activation of β2 -adrenoceptor, for example, to a relaxation of the bronchial tubes, the uterus and the intestine. In the blood vessels of the β2 - adrenoceptor is the dominant β - adrenoceptor. He is also primarily responsible for the relaxant action of adrenaline component and thus an opponent of α1 -adrenoceptors. At the vasorelaxation not only the β2 - adrenergic receptors of the smooth muscle of blood vessels, but also of the nitric oxide -releasing endothelial cells are involved.

In the fat cells and β2 -adrenoceptors in addition to the β3 -adrenoceptors in the adrenaline -induced mobilization and the reduction of fat reserves involved (lipolysis ).

Pharmacology

The β2 - adrenoceptor is one of the pharmacologically significant targets for drug development. In addition to the endogenous ligands epinephrine and norepinephrine find particularly synthetic agonist therapeutic use. These are, for example clenbuterol, fenoterol, reproterol, salbutamol, salmeterol and terbutaline, for the treatment of bronchial asthma and other respiratory diseases. In the β2 - adrenoceptor agonists are obstetrics, such as fenoterol, used as tocolytics. The lipolytic effect of β2 and muskelanabole - adrenoceptor is an illegal application in animal breeding and the doping in competitive sports.

In contrast to the agonists of the β2 - adrenergic receptor selective antagonists have no therapeutic value. Non-selective beta-blockers, which block both β1 - and β2 -adrenoceptors, such as propranolol, are used in treatment of hypertension, heart failure and coronary heart disease application.