Disease relevance of HRH3

• Here, we report the determination of the structure of the human histamine H(3) receptor gene (HRH3) and the identification of a missense mutation (Ala280Val) in a patient with Shy-Drager syndrome [1].
• In Parkinson's disease, histamine innervation and histamine H3 receptor expression in SNr may be increased [2].
• Pretreatment with a histamine H3 receptor agonist alpha-methylhistamine (1 mg and 2 mg/kg/i.p.), that inhibits histamine synthesis and release in the CNS, thwarted edema formation, BSCB breakdown, and SCBF disturbances after SCI [3].
• Therapeutic potential of histamine H3 receptor agonist for the treatment of obesity and diabetes mellitus [4].
• The inhibition was reversed by micromolar concentrations of the histamine H3 receptor antagonist thioperamide and was sensitive to cholera or pertussis toxin treatment [5].

Psychiatry related information on HRH3

• The histamine H3 receptor as a novel therapeutic target for cognitive and sleep disorders [6].

High impact information on HRH3

• Decreased intracellular calcium mediates the histamine H3-receptor-induced attenuation of norepinephrine exocytosis from cardiac sympathetic nerve endings [7].
• Purification of a histamine H3 receptor negatively coupled to phosphoinositide turnover in the human gastric cell line HGT1 [5].
• These findings provide the first evidence for solubilization, purification, and molecular mass characterization of the histamine H3 receptor protein and for the negative coupling of this receptor phosphatidylinositol turnover through a so far unidentified G protein [5].
• The histamine H3 receptor agonist (R)alpha-methylhistamine (MeHA) inhibited, in a nanomolar range, basal and carbachol-stimulated inositol phosphate formation in the human gastric tumoral cell line HGT1-clone 6 [5].
• Selective histamine H3 receptor antagonists for treatment of cognitive deficiencies and other disorders of the central nervous system [8].

Chemical compound and disease context of HRH3

• Thus, we tested whether the histamine H3 receptor agonists immepip and imetit can alleviate LID in the MPTP-lesioned marmoset model of Parkinson's disease [9].
• Histamine H3 receptor agonists reduce L-dopa-induced chorea, but not dystonia, in the MPTP-lesioned nonhuman primate model of Parkinson's disease [9].

Biological context of HRH3

• The deduced amino acid sequence showed about 40% identity to that of the human histamine H3 receptor, HH3R [10].
• Transfection of GPCR97 into a variety of cell lines conferred an ability to inhibit forskolin-stimulated cAMP formation in response to histamine, but not to acetylcholine or any other biogenic amine [11].
• As part of a directed effort to discover novel G protein-coupled receptors through homology searching of expressed sequence tag databases, we identified a partial clone (GPCR97) that had significant homology to biogenic amine receptors [11].
• In the present paper we report the genomic organization of the human histamine H3-receptor gene, which consists of four exons spanning 5.5 kb on chromosome 20 [12].
• Increased concentrations of histamine and its metabolite, tele-methylhistamine and down-regulation of histamine H3 receptor sites in autopsied brain tissue from cirrhotic patients who died in hepatic coma [13].

Anatomical context of HRH3

• In contrast, histamine H3 receptor activation hyperpolarized and inhibited SNr inhibitory projection neurons, thus decreasing the intensity of basal ganglia output [2].
• Due to its strong basicity and polarity the highly potent and selective histamine H3-receptor agonist (R)-alpha-methylhistamine hardly penetrates biological membranes and is furthermore rapidly inactivated in vivo [14].
• Photoperiodic regulation of histamine H3 receptor and VGF messenger ribonucleic acid in the arcuate nucleus of the Siberian hamster [15].
• The peripheral histamine H3 receptor is a presynaptic heterologous receptor located on postganglionic sympathetic nerve fibers innervating sympathetic effector systems such as blood vessels and the heart [16].
• Contractility studies were conducted to evaluate the effect of histamine H3 receptor activation on sympathetic vasoconstriction in surgically isolated human nasal turbinate mucosa [16].

Associations of HRH3 with chemical compounds

• These observations indicate that the clone is a distinct histamine receptor from HH3R, and thus is named HH4R [10].
• The selective histamine H3 receptor antagonist thioperamide abolished the inhibitory effect of histamine [17].
• Neither the histamine H2 receptor agonist dimaprit (1 mM) nor the histamine H3 receptor agonist S-(+)-alpha-methyl histamine (1 mM) altered short circuit current [18].
• Responses to histamine were significantly reduced by the histamine H1 receptor antagonist mepyramine (1-10 microM) but not altered by the histamine H2 receptor antagonist cimetidine (100 microM) or by the histamine H3 receptor antagonist thioperamide (1 microM) [18].
• 2-(4-alkylpiperazin-1-yl)quinolines as a new class of imidazole-free histamine H3 receptor antagonists [19].

Regulatory relationships of HRH3

• We show mRNA for the histamine H3 receptor is down-regulated and VGF is up-regulated in the dmpARC in hamsters switched from long- to short-day photoperiod [15].

Other interactions of HRH3

• The histamine H3 receptor is an attractive G protein-coupled receptor drug target that regulates neurotransmission in the central nervous system and plays a role in cognitive and homeostatic functions [20].

Analytical, diagnostic and therapeutic context of HRH3

• Low expression of HH4R was detected in a wide variety of peripheral tissues by RT-PCR; however, in contrast with HH3R, expression was not detected in the brain [10].
• Enantiomeric separations by cyclodextrin-modified capillary electrophoresis of chiral carbamates containing a 4-substituted imidazole heterocycle, pharmacologically acting as histamine H3-receptor antagonists, were carried out [21].
• RESULTS: In this study we show, using in situ hybridization, that histamine H3 receptor mRNA increases in the cortex, caudate nucleus and putamen during hibernation, an increase that is accompanied by elevated receptor binding in the cerebral cortex, globus pallidus and substantia nigra [22].

References