Abstract
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.
Footnotes
P.P. received financial support from The Academy of Finland, The Sigrid Juselius Foundation, The Finnish Foundation for Alcohol Studies and (previously) a lecture compensation from Abbot Laboratories. P.C. received financial support from Gedeon Richter and GSK, compensation from Abbott Laboratories for a lecture and consultancy support from Ziarco Pharma Ltd. M.C. is an employee of AbbVie. R.G. received support from DFG [German Research Foundation GU434/6-1] and project support by Johnson & Johnson. R.L. received financial support from the Netherlands Organisation for Scientific Research (NWO), Abbott Laboratories, Pfizer, and UCB Pharma, and is a founder of Griffin Discoveries. W.L.S.L. is a founder of Ziarco Pharma Limited. R.L.T. is an employee of Janssen Research & Development. H.S. is one of the inventors of pitolisant. NC-IUPHAR is supported in part by Wellcome Trust Grant 099156/Z/12/Z. Original work by P.P., P.C., R.G., R.L., and H.S. was supported by European Cooperation in Science and Technology Action BM0806.
This review is dedicated to the memory of Professor Sir James Black, FRS, Nobel laureate, who died on 22 March 2010, and Professor Walter Schunack, who died on 6 April 2011.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics