H4 receptor
Encyclopedia
The histamine H4 receptor is, like the other three histamine receptors, a member of the G protein-coupled receptor
superfamily.
-induced pleurisy
mouse model. It is also expressed in the colon, liver, lung, small intestine, spleen, testes, thymus, tonsils, and trachea.
chemotaxis
. It seems to do this by the mechanism of Gi-coupled decrease in cAMP.
A second rhodopsin based structural model of the H4 receptor was successfully used for the identification of novel H4 ligands.
Recent advancements in GPCR crystallization, in particular the determination of the human histamine H1 receptor in complex with doxepin will likely increase the quality of novel structural H4 receptor models.
and allergy
may be treated.
The highly selective histamine H4 antagonist VUF-6002 is orally active and inhibits the activity of both mast cell
s and eosinophils in vivo, and has antiinflammatory and antihyperalgesic
effects.
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
superfamily.
Tissue distribution
H4 is highly expressed in bone marrow and white blood cells and regulates neutrophil release from bone marrow and subsequent infiltration in the zymosanZymosan
Zymosan is a glucan with repeating glucose units connected by β-1,3-glycosidic linkages. It binds to TLR 2.Zymosan is prepared from yeast cell wall and consists of protein-carbohydrate complexes. It is used to induce experimental sterile inflammation...
-induced pleurisy
Pleurisy
Pleurisy is an inflammation of the pleura, the lining of the pleural cavity surrounding the lungs. Among other things, infections are the most common cause of pleurisy....
mouse model. It is also expressed in the colon, liver, lung, small intestine, spleen, testes, thymus, tonsils, and trachea.
Function
They have been shown to mediate mast cellMast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
chemotaxis
Chemotaxis
Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
. It seems to do this by the mechanism of Gi-coupled decrease in cAMP.
Structure
The 3D structure of the H4 receptor has not been solved yet due to the difficulties of GPCR crystallization. Some attempts have been made to develop structural models of the H4 receptor for different purposes. The first H4 receptor model was built by homology modelling based on the crystal structure of bovine rhodopsin. This model was used for the interpretation of site-directed mutagenesis data, which revealed the crucial importance of Asp94 (3.32) and Glu182 (5.46) residues in ligand binding and receptor activation.A second rhodopsin based structural model of the H4 receptor was successfully used for the identification of novel H4 ligands.
Recent advancements in GPCR crystallization, in particular the determination of the human histamine H1 receptor in complex with doxepin will likely increase the quality of novel structural H4 receptor models.
Agonists
- 4-Methylhistamine4-Methylhistamine4-Methylhistamine is a histamine agonist selective for the H4 subtype....
- VUF-8430VUF-8430VUF-8430 is a histamine agonist selective for the H4 subtype....
(2-[(Aminoiminomethyl)amino]ethyl carbamimidothioic acid ester)
Antagonists
- ThioperamideThioperamideThioperamide is a potent and selective histamine H3 antagonist that is capable of crossing the blood-brain barrier....
- JNJ 7777120JNJ 7777120JNJ-7777120 is a drug being developed by Johnson & Johnson Pharmaceutical Research & Development which acts as a potent and selective antagonist at the histamine H4 receptor. It has antiinflammatory effects, and has been demonstrated to be superior to traditional antihistamines in the treatment of...
- VUF-6002VUF-6002VUF-6002 is a drug which acts as a potent and selective antagonist at the histamine H4 receptor. It has antiinflammatory and analgesic effects in animal studies of acute inflammation....
(1-[(5-Chloro-1H-benzimidazol-2-yl)carbonyl]-4-methylpiperazine) - A987306
- A943931
Therapeutic potential
By inhibiting the H4 receptor, asthmaAsthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
and allergy
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
may be treated.
The highly selective histamine H4 antagonist VUF-6002 is orally active and inhibits the activity of both mast cell
Mast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
s and eosinophils in vivo, and has antiinflammatory and antihyperalgesic
Hyperalgesia
Hyperalgesia is an increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves. Temporary increased sensitivity to pain also occurs as part of sickness behavior, the evolved response to infection.-Types:...
effects.