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Distinct pharmacology of rat and human histamine H-3 receptors: role of two amino acids in the third transmembrane domain

Ligneau, X; Morisset, S; Tardivel-Lacombe, J; Gbahou, F; Ganellin, CR; Stark, H; ... Arrang, JM; + view all (2000) Distinct pharmacology of rat and human histamine H-3 receptors: role of two amino acids in the third transmembrane domain. British Journal of Pharmacology , 131 (7) 1247 - 1250.

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Abstract

Starting from the sequence of the human histamine H-3 receptor (hH(3)R) cDNA, we have cloned the corresponding rat cDNA. Whereas the two deduced proteins show 93.5% overall homology and differ only by five amino acid residues at the level of the transmembrane domains (TMs), some ligands displayed distinct affinities. Thioperamide and ciproxifan were about 10 fold more potent at the rat than at the human receptor, whereas FUB 349 displayed a reverse preference. Histamine, (R)alpha - methylhistamine, proxyfan or clobenpropit were nearly equipotent at H-3 receptors of both species. The inverse discrimination patterns of ciproxifan and FUB 349 were partially changed by mutation of one amino acid (V122A), and fully abolished by mutation of two amino acids (A119T and V122A), in TM3 of the rH(3)R located in the vicinity of Asp(114) purported to salt-link the ammonium group of histamine. Therefore, these two residues appear to be responsible for the distinct pharmacology of the H3R in the two species

Type:Article
Title:Distinct pharmacology of rat and human histamine H-3 receptors: role of two amino acids in the third transmembrane domain
Additional information:Journal Article DEC 380RR Arrang JM Ctr Paul Broca, INSERM, U109, Unite Neurobiol & Pharmacol Mol, 2ter Rue Alesia, F-75014 Paris, France BRIT J PHARMACOL
Keywords:ACID, Acids, AFFINITIES, affinity, agonists, amino acid, Amino Acids, Brain, cDNA, ciproxifan, clobenpropit, discrimination, domain, France, FUB 349, G protein-coupled receptors, H-3, H-3 receptor, H-3-RECEPTOR ANTAGONIST, H3, Histamine, inhibition, LEVEL, LIGAND, ligands, Mutation, Pattern, PATTERNS, pharmacology, POTENT, PROTEIN, Proteins, rat, Receptor, receptors, release, SEQUENCE, site-directed mutagenesis, thioperamide, [I-125]iodoproxyfan
UCL classification:UCL > School of BEAMS > Faculty of Maths and Physical Sciences > Chemistry

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