Histamine H1 receptor

• OMIM: 600 167
• UniProt: P35367

The histamine H1 receptor ( H1 receptor short ) is a protein from the family of histamine receptors that can be activated by the body's own tissue hormone histamine. In the human body of the H1 receptor is widely distributed and occurs, for example in the cell membrane of cells of the immune system such as mast cells, smooth muscle and in nerve cells. Among the main features of this receptor include the teaching of allergy-like effects of histamine and neurotransmission. Is a G -protein coupled receptor.

Biochemistry

Genetics

The human H1 receptor was first cloned in 1995. It is encoded by a gene on chromosome 3 in the 3q25 locus. The coding DNA sequence is intro free.

Protein structure

The H1 - receptor protein in humans consists of 487 amino acids. Using X-ray crystal structure analysis of a predicted structure with seven helical transmembrane domains ( heptahelikaler receptor) could be confirmed. The receptor protein comprises in analogy to the muscarinic acetylcholine receptors over a distinct second intracellular loop, but only over a short intracellular C- terminal residue

Signal transduction

At a molecular level resulting stimulation of H1 receptors to activation of Gq/11-Proteinen and activation of phospholipase C is connected to the release of Ca2 from intracellular stores. As a result, various intracellular signal transduction pathways are activated that lead to a contraction of smooth muscle cells or to a release of inflammatory mediators, such as interleukins. The liberated calcium triggers, inter alia, the release of nitric oxide from the vascular endothelium, which causes vasodilation, eg in the course of an allergic reaction.

Function

Activation of H1 receptors is mainly responsible for the observed allergy-like effects of histamine. These include itching and pain, contraction of smooth muscles in the bronchi and large blood vessels ( diameter greater than 80 microns ), and expansion of small blood vessels associated with hives and rash. In the central nervous system via activation of histamine H1 receptors in the initiation of vomiting and the regulation of the sleep -wake rhythm is involved and has an antidepressant and anticonvulsant activity. H1 receptors are also involved in regulating the release of hormones, such as adrenaline involved.

Pharmacology

Antagonists of histamine at the H1 receptor (H1- antihistamines) are used therapeutically for the treatment of allergic disorders, sleep disturbance and vomiting. Based on the number used in therapy substances is the H1 - receptor par with the glucocorticoid receptor, the pharmacologically important target molecule (target). General three generations of H1 - antihistamines can be distinguished today:

• H1 - antihistamines 1st generation (eg, diphenhydramine and doxylamine ) are rarely used today because of their sedative effect in the treatment of allergic disorders. You will find rather for the treatment of insomnia as well as nausea and vomiting use.

• H1 - antihistamines 2nd generation (such as cetirizine, loratadine and terfenadine ) have a weaker sedative effect than the agents of the first generation. You are selectively used as anti-allergic agents.

• H1 - antihistamines 3rd generation (such as levocetirizine, desloratadine and fexofenadine ) represent a further development of the H1 antihistamines 2nd generation dar. Frequently they were developed for strategic reasons, a therapeutic gain over their predecessors mostly missing.

In contrast to the H1-receptor antagonists, the H1-receptor agonists have a low therapeutic importance. Only betahistine, an analogue of histamine with H1 and H3 receptor-antagonistic effect rezeptoragonistischer is used in the treatment of vertigo. Selective H1-receptor agonists, such as Histaprodifen, find therapeutic application.