Transmembrane domains histamine receptors

Histamine is an autacoid present at high levels in lungs, skin, and the GI tract and released from mast cells and basophils by type I hypersensitivity reactions, drugs, venoms, and trauma. Histamine receptors are of the serpentine family, with seven transmembrane-spanning domains with G-protein-coupled second messenger effectors. 

Histamine receptors are of the serpentine family, with seven transmembrane-spanning domains with G-protein-coupled second messenger effectors. 

Ligneau, X., Morisset, S., Tardivel-Lacombe, T., Ghabou, F., Ganellin, C.R., et at. (2000) Distinct pharmacology of rat and human histamine H3 receptors role of two amino acids in the third transmembrane domain. Br. J. Pharmacol. 131 1247-1250. 

The H2 receptor is a 359-amino-acid protein in humans. It has some features similar to the Hi protein (e.g., N-terminal glycosylation sites) and phosphorylation sites in the C-terminal. An aspartic acid residue in the third transmembrane loop appears to be critical to agonist and antagonist binding, and threonine/aspartate and tyrosine/aspartate couples in the fifth transmembrane domain appear to be important for interaction of the imidazole part of the histamine molecule. It is positively coupled via Gas to activate adenylyl cyclase for synthesis of cyclic adenosine monophosphate (cAMP) as a second messenger. In some systems, it is coupled through Gq proteins to stimulate phospholipase C. It appears in some cells that other processes, such as breakdown of phosphoinositides, control of intracellular calcium ion levels, and phospholipase A2 activity, can be regulated by other cAMP-independent pathways. 

The amino add sequence of the Hz receptor, with the transmembrane domains and the glycosylation site on the outside. The seven transmembrane segments (TM1-7) are shown, as well as a histamine antagonist (colored chemical molecule) binding between TM3 and TM5. 

Leurs R, Smit MJ, Meeder R, Ter Laak AM, Timmerman H. Lysine 200 located in the fifth transmembrane domain of the histamine Hi receptor interacts with histamine but not with all Hi agonists. Biophysical Res Comm. 1995 214 110-117. 

Nederkoom PHJ, van Gelder EM, Donne-Op den Kelder GM, limmerman H. The agonistic binding site at the H2 receptor II. Theoretical investigations of histamine binding to the seven a-heUcal transmembrane domain. / Comp Aided Mol Des. 1996 10 479-489. 

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