Disease relevance of HRH1

• In the skin the cardinal features of urticaria (vasodilation, vascular permeability, and pruritus) can be mediated by stimulation of the H1 receptor [1].
• Of the four cardinal signs of asthma (bronchospasm, edema, inflammation, and mucus secretion), histamine is capable of mediating the first two through its H1 receptor and mucus secretion through its H2 receptor [1].
• In anaphylaxis histamine H1-receptor stimulation can mediate vascular permeability, smooth muscle contraction, and tachycardia, whereas H2-receptor stimulation can mediate mucus secretion [1].
• Of the five cardinal signs of allergic rhinitis (pruritus, mucosal edema, sneezing, mucus secretion, and late-phase inflammatory reactions), histamine is capable of mediating the first three through its H1 receptor [1].
• Characteristics of the binding of [3H]-mepyramine to intact human U373 MG astrocytoma cells: evidence for histamine-induced H1-receptor internalisation [2].

Psychiatry related information on HRH1

• The histamine receptor H1 antagonist diphenhydramine, the antimalarial drug amodiaquine, the antifolate drug metoprine, and the anticholinesterase drug tacrine (an early drug for Alzheimer's disease) are surprisingly all potent HNMT inhibitors, having inhibition constants in the range of 10-100nM [3].
• Unlike the classic antihistamines, the new H1-receptor antagonists do not block cholinergic or central H1 receptors and thus do not produce the side effects, such as sedation, impaired psychomotor performance, and excessive mucosal drying, that are commonly associated with the older agents [4].
• Selective histamine-H1 receptor antagonists inhibit adenosine 5'-monophosphate (AMP)-induced bronchoconstriction by greater than 80% when expressed as a percentage inhibition of the FEV1 time-response curve following inhalation of the provocation concentration of AMP required to produce a 20% decrease in FEV1 from baseline (PC20) [5].
• Individual differences in central nervous system response to antihistamines (H1-receptor antagonists) [6].
• Within the central nervous system (CNS), interference with normal histamine binding to the H1 receptor is associated with drowsiness and psychomotor impairment [7].

High impact information on HRH1

• In contrast, in cultures with IL-13 plus anti-CD58 mAb, histamine-induced enhancement was blocked by dimaprit (H1 receptor antagonist), and was inhibited by anti-IL-6 mAb [8].
• The histamine-mediated decrease in TNF-alpha synthesis was not affected by indomethacin, nor by diphenhydramine, an H1 receptor antagonist, but was reversed by cimetidine or ranitidine, H2 receptor antagonists, in a dose-dependent manner [9].
• Ca(2+) imaging studies revealed that PLCbeta3 specifically mediates histamine-induced calcium responses through the histamine H1 receptor in cultured sensory neurons [10].
• These results demonstrate that PLCbeta3 is required to mediate "itch" sensation in response to histamine acting on the histamine H1 receptor in C-fiber nociceptive neurons [10].
• Diphenhydramine, an H1 receptor antagonist, had no effect [11].

Chemical compound and disease context of HRH1

• 3 Histamine H1-receptor agonists, 2-methyl-histamine and 2-pyridyl-ethylamine, also produced hypothermia which could be blocked by mepyramine [12].
• Cimetidine may be effective in patients with recalcitrant acute allergic urticaria who are already being treated with H-1-receptor-blocking antihistamines [13].
• All five had persistent hives after treatment with at least epinephrine and diphenhydramine (Benadryl, an H-1 receptor blocker) [13].
• Twelve patients with nonexertional chest pain and nonobstructive fixed coronary disease (less than 50% luminal diameter narrowing) were given histamine to investigate the potential role (coronary artery H1 receptor agonism) of the endogenous agent in producing coronary artery spasm (CAS) [14].
• Eighteen patients with atopic dermatitis were randomly chosen for a clinical trial to compare the action of the H2 receptor antagonist cimetidine in combination with the H1 receptor antagonist chorpheniramine against the chlorpheniramine alone and against placebo [15].

Biological context of HRH1

• Both the coding region of the H1 receptor gene and its promoter region were independently mapped to chromosome 3p25 [16].
• Here we report the isolation and characterization of genomic clones containing the 5' flanking (regulatory) region of the human histamine H1 receptor gene [16].
• Immediately upstream of the transcription start site a fragment of 1.85 kb was identified that showed promoter activity when placed upstream of a luciferase reporter gene and transiently transfected into cells expressing the histamine H1 receptor [16].
• The results suggested that two groups, i.e., residues Thr140 and Thr142, and residues Ser396 and Ser398, independently contributed to H1R downregulation [17].
• A cDNA clone for the histamine H1 receptor was isolated from a human lung cDNA library; it encoded a protein of 487 amino acids which showed characteristic features of G-protein-coupled receptors [18].

Anatomical context of HRH1

• Recent reports showed effects of histamine on human monocyte-derived dendritic cells (MoDC) mediated primarily via histamine H1 receptors (H1R) and H2R [19].
• We have assigned the human histamine H1-receptor gene to chromosome 3 by Southern blot analysis of a chromosome mapping panel constructed from human-hamster somatic cell hybrids [20].
• This cell line provides a model for analyzing the biochemical responses of H1 receptor-mediated reactions in peripheral tissues [21].
• The human H1-receptor cDNA was transfected into Chinese hamster ovary cells (CHO) via an eukaryotic expression vector; the receptor protein present on cell membranes specifically bound [3H]mepyramine with a Kd of 3.7 nM [18].
• Northern blot analysis showed that H1 receptor mRNAs visualized as two bands with 3.0-kilobase and 3.5-kilobase nucleotides were expressed in peripheral tissues such as placenta, lung, skeletal muscle, and kidney and that only one species with 3.5-kilobase nucleotides was present in the brain [22].

Associations of HRH1 with chemical compounds

• The unretained fraction of heparin (HRH1) had a low affinity for AT-III [23].
• Functional exploration of these receptors was performed by monitoring the increase of intracellular calcium levels (H1R), cyclic adenosine monophosphate formation (H2R), F-actin polymerization, and IL-12p70 production [24].
• The mean Kd for the binding of [3H]-mepyramine to the saturable component, 2.5 +/- 0.4 nM, was in close agreement with the value of 3.5 nM for mepyramine derived from inhibition of histamine H1-receptor-mediated inositol phosphate formation in U373 MG cells [2].
• Human histamine H1 receptor (H1R) contains five possible phosphorylation residues (Thr140, Thr142, Ser396, Ser398 and Thr478) and the substitution of all these five residues to alanine completely impairs agonist-induced receptor downregulation [17].
• Two threonine residues and two serine residues in the second and third intracellular loops are both involved in histamine H1 receptor downregulation [17].

Physical interactions of HRH1

• Small H1R agonists and 2-phenylhistamines interacted differentially with human and guinea pig H2R in terms of potency and efficacy, respectively [25].

Regulatory relationships of HRH1

• Recent investigations suggest that H1R signaling on lymphocytes may enhance whereas activation of the H2R may inhibit lymphocyte responses [26].
• However, our inability to reconstitute efficient coupling of PAFR and H1R to mammalian Gqalpha indicated that a large portion of the expressed G protein was functionally inactive [27].
• Selective activation of H2 receptors by combined infusion of HA and the H1 receptor antagonist mepyramine inhibited PRL secretion compared to the effect of NaCl [delta PRL, -55 +/- 23 (+/- SEM) vs. -20 +/- 17 microIU/ml; P less than 0.01; n = 6) [28].
• The histamine-enhanced expression of E-selectin and ICAM-1 was inhibited by the histamine H1 receptor antagonists, mepyramine and diphenhydramine [29].
• H1 receptor antagonists inhibited DNA synthesis in vitro and ECL neoplasia in vivo without altering gastrin levels [30].

Other interactions of HRH1

• Histamine receptor immunoreactivity (H1R, H2R, H3R, H4R) was found in situ and in vitro [31].
• We coexpressed hH1R and gpH1R with regulators of G-protein signaling in Sf9 insect cells and analyzed the GTPase activity of Gq-proteins [25].
• The H1 receptor is involved not only in allergic inflammatory reactions but also in augmentation of helper T cell (Th)1 responses, whereas H2 receptor suppresses Th responses and participates in immune tolerance through interleukin-10 and transforming growth factor-beta [32].
• Inhibition of H1 receptors attenuates the rise in CVC to exogenous VIP (P < 0.05); however, combined H1-receptor inhibition and NO synthase inhibition further reduced VIP-mediated vasodilation compared with either H1 inhibition or NO synthase inhibition alone (P < 0.05) [33].
• Using H1 receptor (cetirizin and loderix) and H2 receptor (cimetidine and ranitidine) specific antagonists, an H1-dependent stimulation of IL-6 binding by CESS cells was found [34].

Analytical, diagnostic and therapeutic context of HRH1

• METHODS: Expression of histamine H1 and H2 receptors (H1R and H2R) on MoDCs was assessed by means of RT-PCR and flow cytometry [24].
• Northern blot analysis indicated the presence of two histamine H1 receptor mRNAs of 3.5 kb and 4.1 kb in various human tissues and an additional mRNA of 4.8 kb restricted to the human brain [18].
• The human H1 receptor gene was mapped to the chromosome 3p25 by the fluorescence in situ hybridization method [22].
• Molecular cloning of the human histamine H1 receptor gene [22].
• Conversely, the distribution of histamine H1 receptors on different lymphocyte subsets has been thoroughly analyzed using specific radioligands, whereas the functional significance of histamine H1 receptor ligation on lymphocytes has not been fully elucidated yet [26].

References