Royal Highness

Royal Highness (abbreviation HRH) is a style used to address or refer to some members of royal families, usually princes other than monarchs and their female consorts (i.e., kings and queens). When used as a direct form of address, spoken or written, it takes the form "Your Royal Highness". When used as a third-person reference, it is gender-specific (Her Royal Highness or His Royal Highness, both abbreviated HRH) and, in plural, Their Royal Highnesses (TRH).

Holders of the style Royal Highness generally rank below holders of the style Imperial Highness, but above those addressed as Grand Ducal Highness, Highness, Serene Highness and some other styles.

Origin

By the 17th century, all local rulers in Italy adopted the style Highness, that was once used by kings and emperors only. According to Denis Diderot's Encyclopédie, the style of Royal Highness was created on the insistence of Archduke Ferdinand of Austria, Cardinal-Infante of Spain, a younger son of King Philip III of Spain. The Archduke was travelling through Italy on his way to the Low Countries and, upon meeting Victor Amadeus I, Duke of Savoy, refused to address him as Highness unless the Duke addressed him as Royal Highness. Thus, the first use of the style Royal Highness was recorded in 1633. Gaston, Duke of Orléans, younger son of King Henry IV of France, encountered the style in Brussels and assumed it himself. His children later used the style, considering it their prerogative as grandchildren of France.

Histamine H4 receptor

The histamine H₄ receptor is, like the other three histamine receptors, a member of the G protein-coupled receptor 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 zymosan-induced pleurisy mouse model. It is also expressed in the colon, liver, lung, small intestine, spleen, testes, thymus, tonsils, and trachea.

Function

The Histamine H4 receptor has been shown to be involved in mediating eosinophil shape change and mast cell chemotaxis. This occurs via the βγ subunit acting at phospholipase C to cause actin polymerisation and eventually chemotaxis.

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.

Histamine H1 receptor

The H₁ receptor is a histamine receptor belonging to the family of Rhodopsin-like G-protein-coupled receptors. This receptor, which is activated by the biogenic amine histamine, is expressed throughout the body, to be specific, in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. The H₁ receptor is linked to an intracellular G-protein (G_q) that activates phospholipase C and the phosphatidylinositol (PIP2) signalling pathway. Antihistamines, which act on this receptor, are used as anti-allergy drugs. The crystal structure of the receptor has been determined (shown on the right) and used to discover new histamine H₁ receptor ligands in structure-based virtual screening studies.

Role in inflammation

The expression of NF-κB, the transcription factor that regulates inflammatory processes, is promoted by the constitutive activity of the H₁ receptor as well as by agonists that bind at the receptor.H₁-antihistamines have been shown to attenuate NF-κB expression and mitigate certain inflammatory processes in associated cells.