Histamine receptor characterization

Betazole (683) has been used as a chemical control substance for pharmacological characterization of histamine receptors (B-80MI40406), and shows a relative selective activity towards the H2-receptor. Betazole hydrochloride is used to diagnose impairment of the acid-producing cells of the stomach. 

S Molecular cloning and characterization of a novel 62 type of histamine receptor preferentially expressed in leukocytes. J Biol Chem 2000 275 36781. 

Oda, T., Morikawa, N., Saito,Y., Masuho,Y. and Matsumoto, S. Molecular cloning and characterization of novel type of histamine receptor preferentially expressed in leukocytes. /. Biol. Chem. 275 36781-36786, 2000. 

Nakamura T, Itadani H, Hidaka Y, Ohta M, Tanaka K Molecular cloning and characterization of a new human histamine receptor, HH4R. Biochem Biophys Res Common 2000 279 615-620. 

Histamine exerts its biologic actions by combining with specific cellular receptors located on the surface membrane. The four different histamine receptors thus far characterized are designated H -H4 and are described in Table 16-1. Unlike the other amine transmitter receptors discussed previously, no subfamilies have been found within these major types, although different splice variants of several receptor types have been described. 

The term "H3 receptor" has been coined by Arrang et al.1 H3 receptors are located on paracrine cells and on neurones activation of H3 receptors usually causes inhibition of the release of the respective mediator or neurotransmitter. The receptor characterized by Arrang et al.1 is an example of an autoreceptor, i.e. of a receptor via which the transmitter released from a given neurone influences its own release. H3 receptor-mediated inhibition of the release of transmitters other than histamine has also been described such receptors are known as heteroreceptors. The present review will focus on H3 heteroreceptors in the central nervous system (CNS) in separate chapters of this book, H3 autoreceptors, H3 heteroreceptors in the neuroendocrine system as well as H3 receptor-mediated modulation of transmitter release in vivo will be considered. A separate article will also deal with H3 heteroreceptors in peripheral tissues although an example of an H3 receptor in the retina will be covered in our chapter, due to the close relationship between CNS and retina2. 

Bull, H.A., Courtney, P.F., Rustin, M.H.A., Dowd, P.M., 1992. Characterization of histamine receptor sub-types regulating prostacyclin release from human endothelial cells. Br. J. Pharmacol. 107, 276-281. 

Cardell L.O., Edvinsson, L., 1994. Characterization of the histamine receptors in the guinea-pig lung evidence for relaxant histamine H3 receptors in the trachea. Br. J. Pharmacol. Ill, 445-454. 

Korte, A., Myers, J., Shih, N.Y., Egan, R.W., Clark, M.A., 1990. Characterization and tissue distribution of H3 histamine receptors in guinea pigs by N -methylhistamine. Biochemical. Biophysical. Res. Comm. 168, 979-986. 

Raible, D.G., Lenahan, T., Fayvilevich, Y., Kosinski, R., Schulman, E.S., 1994 Pharmacological characterization of a novel histamine receptor on human eosinophils. Am. J. Respir. Crit. Care Med. 149, 1506-1511. 

Cumming, P., Shaw, C. and Vincent, S.R. (1991). High affinity histamine binding site is the H3-receptor - characterization and autoradiographic localization in rat brain. Synapse 8, 144-151. 

Ganellin, C. R. Characterization and distribution of histamine receptors. In The chemical regulation of biological mechanisms Creighton, A. M. Turner, S. Eds. Royal Society of Chemistry London, U.K., 1982 pp. 1-15. 

A new histamine receptor, the H4 subtype, was fint reported in 2000 and characterized as a 390-amino acid. G,-coupled protein with 40% identity to the H3 receptor. " This new receptor exhibits a very restricted localization expression is primarily found in intestinal tissue, spleen, thymus, and immune active cells, such as T cells, neutrophils, and eosinophils, which sugge.sts an important role for Hi receptors in the regulation of immune function. 

Histamine is an autacoid released from mast cells and basophils by type I hypersensitivity reactions or under the influence of drugs, venoms, or trauma. Histamine receptors are the G-protein-coupled, seven-transmembrane type. Three different receptors are recognized the well-characterized H, and Hj types and an Hj variant. 

The best known member of this class is ketanserin (Table 2). For more than a decade ketanserin is the most widely used tool to characterize 5-HT2 receptors [7]. Ketanserin displays a high affinity for the 5-HT2A receptor, a moderate affinity for the S-HTjc receptor and a weak affinity for the S-HTjb receptor (Tables 1,2). Ketanserin is not selective for the 5-HTja receptor and binds with high affinity to Ui-adrenoceptors and moderate affinity to histamine receptors [2]. In functional tests ketanserin acts as an antagonist. 

As early as 1966, Ash and Schildd ), using a number of histamine analogues and several histamine-sensitive in vivo and in vitro preparations, succeeded in defining 2 distinct classes of histamine receptors (Hi and Hj ) certain of the agonists which they studied were more active at the former sites, others at the latter. The identification of these receptors in different organs is still far from complete. Some of the receptors thus far characterized are listed in Table 1. 

Toyota, H., Dugovic, C., Koehl, M. et al. (2002). Behavioral characterization of mice lacking histamine H3 receptors. Mol. Pharmacol 62, 389-97. 

Traiffort, E., Pollard, H., Moreau, J. et al. (1992). Pharmacological characterization and autoradiographic localization of histamine H2 receptors in human brain identified with [125I]iodoaminopotentidine. J. Neurochem. 59, 290-9. 

Yates, S. L., Phillips, J. G., Gregory, R. etal. Identification and pharmacological characterization of a series of new 1H-4-substituted-imidazoyl histamine H3 receptor ligands. J. Pharmacol. Exp. Ther. 289 1151-1159,1999. 

Sinkins, W. G., Kandel, M Kandel, S. I., Schunack, W and Wells, J. W. (1993) G protein-linked receptors labeled by [3H]histamine in guinea pig cerebral cortex. I. Pharmacological characterization [corrected]. Mol. Pharmacol. 43, 583-594. 

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