Adrenergic receptor

Adrenoceptors, also adrenergic receptors are receptors which are activated by the natural neurotransmitters adrenaline and noradrenaline, and are thus responsible for the effects mediated by norepinephrine and epinephrine. Adrenoceptors play an important role especially in the sympathetically innervated tissues. In addition adrenoceptors occur for example in the central nervous system and blood platelets.

Classification

Adrenoceptors are G- protein - coupled receptors of class A and have as such a close relationship with the rhodopsin. The nine identified human receptor proteins are divided on the basis of their pharmacological and molecular biological properties into three families:

• α1 - adrenoceptor subtypes with the alpha1A, α1B and α1D, which can be mainly found in blood vessels.
• α2 -adrenoceptors with the subtypes? 2A, alpha 2b and α2C, which can be found for example on platelets and on neurons of the autonomic nervous system and the central nervous system.
• β - adrenoceptor subtypes with β1, β2 and β3, particularly for the regulation of the heart activity ( inotropy, chronotropy and Dromotropie ) and the relaxation of smooth muscle (for example, in the bronchial tubes ) responsible. β2 -adrenoceptors are also expressed on immune cells and play a role in CNS -immune communication.

Moreover, it was based on " α1L " - adrenoceptor as a phenotype of alpha1A - adrenoceptor and a postulated to different pharmacological properties " β4 " - adrenoceptor as low-affinity variant of the β1 - adrenergic receptor. A designated as α2D - adrenoceptor receptor of rodents was found to be the orthologs of the human? 2A - adrenergic receptor.

Structure

All as a seven cell membrane spanning helices, it is assumed for the existing structure adrenoceptors for G -protein coupled receptors. This could be confirmed by X-ray crystallographic data and at least the β1 and the β2 - adrenergic receptor. Just as the rhodopsin adrenoceptors possess an intracellular helix 8 ( HX8 ). In contrast to all other G protein -coupled receptors with a known crystal structure, an additional helix structure in the second extracellular loop ( ECL2 ) was detected near the ligand binding pocket for both β1 - and β2 -adrenoceptors for.

Pharmacology

Drugs that interact with adrenoceptor be used in various ways for drug therapy. In this case, both agonists and antagonists can find application. Adrenaline and noradrenaline itself can be used as an emergency therapeutics.

Inhibitors of α1 -adrenoceptors, which belong to the so-called alpha-blockers, are used especially in the treatment of hypertension. Alpha blockers with selectivity for the alpha1A subtype, such as tamsulosin, have also proven effective in the treatment of benign prostatic hyperplasia. An alpha blocker with selectivity for α2 -adrenoceptors, yohimbine, had a role in the symptomatic treatment of erectile dysfunction. α - sympathomimetic agents acting agonist at α -adrenoceptors, are used inter alia as a nasal spray for decongestion of the nasal mucosa. α2 - adrenoceptor agonists also have a meaning as antihypertensive (blood pressure lowering agent ) and in the symptomatic treatment of glaucoma.

A very wide range of applications have beta-blockers. Particular they are used in the treatment of hypertension, coronary heart disease, chronic heart failure, cardiac arrhythmias, and migraine. For their discovery in 1988 Sir James Whyte Black was honored with the Nobel Prize in Physiology or Medicine. β2 -agonists are used in pulmonary medicine for acute treatment of bronchial asthma and COPD as well as in obstetrics as tocolytics.