Disease relevance of Hrh2

• METHODS: We examined a functional role of inducible histamine in the protection against hepatic injury and lethality in Propionibacterium acnes -primed and lipopolysaccharide-induced hepatitis, using histidine decarboxylase knockout and H2-receptor knockout mice [1].
• In this study, we show that mice lacking histamine H2 receptor (H2RKO) are similar to H1RKO mice in that they develop encephalitogen-specific T-cell responses as assessed by proliferation and IL-2 production and present with less severe acute early-phase experimental allergic encephalomyelitis [2].
• Given that both histamine and adjuvants such as pertussis toxin modulate antigen-presenting cell (APC) maturation and function, including T-cell-polarizing activity, we analyzed the cytokines/chemokines secreted by APCs from wild-type, H1RKO, and H2RKO mice [2].
• However, the H2R-deficient mice exhibited a marked hypertrophy with enlarged folds in gastric mucosa and an elevated serum gastrin level [3].
• Histamine H1 and H2 receptor antagonists accelerate skin barrier repair and prevent epidermal hyperplasia induced by barrier disruption in a dry environment [4].

High impact information on Hrh2

• Mutant mice lacking H2R showed upregulation of both TH1 and TH2 cytokines [5].
• Ranitidine is an H2-receptor antagonist that was released recently for use in the treatment of acute duodenal ulcer disease, Zollinger-Ellison syndrome, and systemic mastocytosis with gastric hypersecretion [6].
• Cultured T cells migrated in response to histamine in vitro, but this was ablated by blockade of H1R but not H2R [7].
• To clarify the physiological roles of histamine H2 receptor (H2R), we have generated histamine H2R-deficient mice by gene targeting [3].
• Abnormal functional and morphological regulation of the gastric mucosa in histamine H2 receptor-deficient mice [3].

Chemical compound and disease context of Hrh2

• METHODS: Male hypergastrinemic mice (INS-GAS mice) were infected with Helicobacter felis and given the CCK2/gastrin receptor antagonist YF476 and/or the histamine H2-receptor antagonist loxtidine for 3 or 6 months [8].
• A single dose of any of the H2R antagonists ranitidine, tiotidine, famotidine, or cimetidine drastically augmented metastasis [9].
• They also question the hypothesis that the bone marrow toxicity of metiamide was related to the thiouridine group in its structure and that substitution of a cyanoguanidine group for the thiouridine moiety represents a structural modification that would avoid bone marrow effects of histamine-H2-receptor antagonists [10].
• The relationship of histamine H2 receptor-bearing suppressor cells with the growth and metastasis of FANFT-induced bladder cancer [11].
• The effects of SK&F 93479, a potent histamine H2-receptor antagonist, on ventricular arrhythmias induced by coronary artery ligation in dogs and rats, and by aconitine infusion in mice were investigated [12].

Biological context of Hrh2

• In many tissues, prolonged absence of histamine induced down-regulation of the H2 receptor subtype [13].
• The present study clearly demonstrates that H2R-mediated signal(s) are required for cellular homeostasis of the gastric mucosa and normally formed secretory membranes in parietal cells [3].
• An interspecific backcross analysis revealed that the mouse H2R gene, designated Hrh2, was located in the central region of chromosome 13 [14].
• A mouse histamine H2 receptor (H2R) gene was isolated from a mouse ES cell genomic DNA library [14].
• Indeed, the entry of these progenitors into S phase that is normally promoted by dimaprit, a specific histamine H2 receptor agonist, is abolished by a preincubation with GM-CSF [15].

Anatomical context of Hrh2

• However, unlike T cells from H1RKO mice, which exhibit a strong Th2 bias, T cells from H2RKO mice do not [2].
• Also, the results presented herein constitute the first molecular evidence for the expression of HA H1 and H2 receptor subtypes in isolated Leydig cells [16].
• Structural and functional characterization of gastric mucosa and central nervous system in histamine H2 receptor-null mice [17].
• A histamine H1 receptor agonist [2-(2-pyridyl)-ethylamine dihydrochloride] had a propensity to activate contrasuppression, whereas an H2 receptor agonist (dimaprit) tended to activate suppressor cells [18].
• The existence of a histamine H2-receptor in the thyroid was investigated [19].

Associations of Hrh2 with chemical compounds

• Inducible histamine protects mice from P. acnes-primed and LPS-induced hepatitis through H2-receptor stimulation [1].
• Furthermore, zolantidine, a selective and hydrophobic H2 receptor antagonist, enhanced the effects of morphine in all nociceptive assays examined [20].
• Histamine H2 receptor antagonists famotidine and cimetidine accelerated the recovery of skin barrier function, but histamine and histamine H2 receptor agonist dimaprit delayed the barrier repair [4].
• Such synergism was abolished by the histamine H2-receptor antagonist famotidine. cAMP involvement in acid secretion was also examined with theophylline, a phosphodiesterase inhibitor, and forskolin, an adenylate cyclase activator [21].
• The H2 receptor antagonist, cimetidine, significantly reduced tumor growth in the animal models while the H1 receptor antagonist, dexchlorpheniramine, had no effect, suggesting that histamine could act via H2 receptor sites [22].

Regulatory relationships of Hrh2

• Histamine induced increase in IL-5 production was inhibited by histamine H2-receptor antagonists, but remained unaffected by H1- or H3-receptor antagonists [23].

Other interactions of Hrh2

• The same dose of Propionibacterium acnes and lipopolysaccharide induced severe hepatitis and high lethality in histidine decarboxylase knockout and H2-receptor knockout mice; the former were rescued by the subcutaneous injection of histamine [1].
• Thus, the blocking of the histamine H1 or H2 receptor may produce antinociception and enhance the orexin A-induced antinociception [24].
• In contrast, the antagonists for GABAA and GABAB receptors injected i.t. showed same nociceptive response with nociceptin and histamine, and their nociceptive responses were significantly blocked by the i.t. co-administration of the H1 receptor antagonists, but not H2 receptor antagonists or ORL-1 receptor antagonists [25].
• Histamine H1 receptor antagonists such as chlorpheniramine and epinastine significantly inhibited nasal allergic symptoms caused by histamine, but the histamine H2 receptor antagonists cimetidine and famotidine showed no effect [26].
• Mice lacking the H2R showed up-regulation of IFN-gamma secretion from CD8+ cells and of IL-4 from CD4+ and CD8+ T cells [27].

Analytical, diagnostic and therapeutic context of Hrh2

• A similar distribution was obtained after perfusion of H1 or H2 receptor agonists coupled to ferritin (2-pyridylethylamine-ferritin [PF], or 4-methylhistamine-ferritin [MF], respectively) [28].
• Two H2 receptor antagonists, cimetidine and ranitidine, reversed the nonspecific immunosuppression of CS induced by burns [29].
• The effects of the histamine H2 receptor antagonist, ranitidine, on parietal cell lineage was studied in the mouse stomach by using light and electron microscopy techniques [30].
• When expressions of histamine H1 (H1R) and H2 (H2R) receptors in DC were analyzed by RT-PCR, both receptors were down-regulated after LPS or TNF-alpha stimulation compared to unstimulated iDC [31].
• These findings suggest that SK&F 93479 lacks non-specific antiarrhythmic activity and that its protective effects against coronary artery ligation may be mediated by its histamine H2-receptor antagonizing action [12].

References