Beta adrenoceptors
A group of phylogenetically related G-protein-coupled receptors (GPCR), which are activated in particular by the hormone adrenaline , are called β-adrenoceptors or beta receptors . They include as the α 1 - and α 2 -adrenoceptors to the family of adrenoceptors and are because of their pharmacological and molecular biological further divided into three subtypes properties: β 1 , β 2 and β 3 . The existence of a fourth subtype, the "β 4 -adrenoceptor", is controversial. X-ray crystal structures of the β 2 and β 1 receptors have been available since October 2007 and June 2008 ; After rhodopsin, they are the second and third GPCR whose structure has been clarified.
Occurrence
β-adrenoceptors are found in high density in the heart , smooth muscles and adipose tissue . In the heart, activation of β 1 -adrenoceptors and, secondarily, activation of the β 2 -subtype lead to an increase in cardiac strength and heart rate . In the kidney there is a β 1 -adrenoceptor-mediated secretion of renin .
In the smooth muscles of the bronchi , the uterus and the blood vessels , the β 2 subtype is the dominant adrenoceptor and leads to relaxation and thus to an expansion of the organs.
The β 3 -adrenoceptor was found predominantly in brown adipose tissue , where it leads to lipolysis and thermogenesis .
The pharmacologically proven in cardiac β 4 -adrenoceptor is present only as an affinity state of the β 1 viewed subtype, as for example in the β 1 - knockout mice no β 4 effects are detectable.
function
Activation of β-adrenoceptors leads to an activation of downstream signal transduction pathways via a coupling of the bound G proteins of the type G s or, furthermore, G i / o . All β-adrenoceptors are able on G s , the adenylyl cyclase activating which the concentration of cAMP in cytosol increased, and this increase in concentration of protein kinase A activated. Signal transduction via G i / o proteins could be demonstrated in particular for β 2 and β 3 adrenoceptors.
The β 1 - adrenoceptors are particularly important in the area of the sinus node and the working muscles of the heart, where they convey positive inotropic , positive lusitropic and positive bathmotropic effects through the sympathetic nervous system . (see also muscle contraction )
In the smooth muscle cells of the bronchioles and the arterioles of the skeletal muscles, β 1 and β 2 receptors mediate the activation of protein kinase A in the same way, which activates the MLCP there by phosphorylation and thus results in an expansion.
pharmacology
β-adrenoceptor agonists
β-adrenoceptor agonists (also β- sympathomimetics ) stimulate β-adrenoceptors. Both β 2 -selective and β 3 -selective adrenoceptor agonists are used therapeutically :
- Salbutamol , salmeterol , terbutaline , clenbuterol , formoterol etc. for the therapy of bronchial asthma .
- Terbutaline as a tocolytic .
- Mirabegron, used to treat overactive bladder.
β 2 -adrenoceptor agonists such as salbutamol and in particular clenbuterol are often misused as doping agents . In the foreground, however, is the application in the therapy of acute asthma attacks . The bronchospasm that occurs can be resolved very quickly by inhalation, so that a rapid improvement occurs.
β-adrenoceptor antagonists
β-adrenoceptor antagonists (also β- sympatholytics ) inhibit the effects caused by adrenaline . They are used therapeutically as beta blockers for high blood pressure , heart failure , angina pectoris and for migraine prophylaxis.
Overview
property | β 1 | β 2 | β 3 | ("Β 4 ") |
---|---|---|---|---|
Signal transduction | G s | G s , G i / o | G s , G i / o | G s |
Agonists | Adrenaline , isoprenaline (isoproterenol), noradrenaline | |||
Selective agonists | Norepinephrine , xamoterol , denopamine | Salbutamol , Salmeterol , Clenbuterol , Terbutaline , Formoterol , Fenoterol | Amibegron , Mirabegron , Solabegron | - |
Antagonists | Propranolol | |||
Selective antagonists | Metoprolol , Bisoprolol , Atenolol , Betaxolol | ICI 118551 | SR59230A | - |
Main function | Increase in heart strength and frequency | Smooth muscle relaxation | Lipolysis | Increase in heart strength and frequency |
literature
- Perry P. Griffin, Manfred Schubert-Zsilavecz, Holger Stark: Inhibitors of beta adrenoceptors. In: Pharmacy in our time . Vol. 33, No. 6, 2004, pp. 442-449. doi: 10.1002 / pauz.200400091
- Cornelia Held, Ralf Kling, Peter Gmeiner: Structure and function of β-adrenergic receptors. In: Pharmakon. Volume 1, No. 5, 2013, pp. 406-412 ( doi : 10.1691 / pn.20130043 ).
Individual evidence
- ^ Georg Löffler, Petro E. Petrides: Biochemistry and Pathobiochemistry . 8th edition. Springer, Berlin 2006
- ↑ Guimarães S, Moura D: Vascular adrenoceptors: an update . In: Pharmacol. Rev. . 53, No. 2, June 2001, pp. 319-56. PMID 11356987 .