Beta adrenoceptors

from Wikipedia, the free encyclopedia
Crystal structure of the β 2 -adrenoceptor in complex with its ligand carazolol

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 :

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

Pharmacology and physiology of β-adrenoceptors
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

Individual evidence

  1. ^ Georg Löffler, Petro E. Petrides: Biochemistry and Pathobiochemistry . 8th edition. Springer, Berlin 2006
  2. ↑ Guimarães S, Moura D: Vascular adrenoceptors: an update . In: Pharmacol. Rev. . 53, No. 2, June 2001, pp. 319-56. PMID 11356987 .