Histamine H1 receptor: Difference between revisions

Allergy symptoms are mostly caused by the release of histamine in response to allergens.  The binding of histamine to the extracellular portion of the H1 receptor triggers a structural change of the transmembrane portion, leading to a change in the C terminal area.  This c terminal region interacts with G proteins, leading to the activation of the Gq signalling pathway, which triggers allergy symptoms like itchy eyeys and runny noses. Many allergy drugs are anti-histamines, in that they bind to the histamine receptor but do not cause the conformational change that leads to a response.

The structure of the H1 histamine receptor bound to an antihistamine, doxepin was published in 2011 <ref>PMID:21697825</ref>. A <scene name='78/784820/N_to_c_rainbow/1'>N-->C rainbow</scene> view colors the N terminus blue and the C terminus red, with the intervening segments paralleling the rainbow (blue, green, yellow, orange, red).  This image is oriented with the transmembrane section at the top and the cytosolic portion below.

<scene name='78/784820/Doxepin/2'>Doxepin</scene> binds among the transmembrane alpha helices.  Binding is stabilized by a number of <scene name='78/784820/Interacting_amino_acids/1'>interactions with amino acids</scene>. Like many G protein coupled receptors, the bottom of the binding pocket contains a conserved <scene name='78/784820/Trp_428/1'>tryptophan</scene> residue. Interestingly, second generation antihistamines take advantage of an anion binding site formed by <scene name='78/784820/Lys/2'>two lysine residues</scene>; in this structure, they interact with a phosphate.