查看文章

Histamine is a developmentally highly conserved autacoid found in most vertebrate tissues. Its physiological functions are mediated by four 7-transmembrane G protein–coupled receptors (H₁R, H₂R, H₃R, H₄R) that are all targets of pharmacological intervention. The receptors display molecular heterogeneity and constitutive activity. H₁R antagonists are long known antiallergic and sedating drugs, whereas the H₂R was identified in the 1970s and led to the development of H₂R-antagonists that revolutionized stomach ulcer treatment. The crystal structure of ligand-bound H₁R has rendered it possible to design new ligands with novel properties. The H₃R is an autoreceptor and heteroreceptor providing negative feedback on histaminergic and inhibition on other neurons. A block of these actions promotes waking. The H₄R occurs on immuncompetent cells and the development of anti-inflammatory drugs is anticipated.