Histamine H1 Receptor Gene Research Articles

Methamphetamine- and 3,4-Methylenedioxymethamphetamine–Induced Behavioral Changes in Histamine H3–Receptor Knockout Mice

Histamine H3 receptors inhibit the release of not only histamine itself, but also other neurotransmitters including dopamine. Previous papers have reported that histaminergic neurons inhibit psychostimulant-induced behavioral changes. To examine whether deficiency in histamine H3 receptors influences psychostimulant-induced behavioral sensitization and reward, we examined locomotor activity, conditioned place preference (CPP), and c-Fos expression in histamine H3 receptor–gene knockout mice (H3KO) and their wild-type (WT) counterparts before and after treatment with methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA). The increase in locomotion induced by treatment with METH or MDMA was lower in histamine H3KO mice than in WT mice, while the locomotor sensitization was developed by METH or MDMA in both strains. However, no significant difference in METH- and MDMA-induced preference scores of CPP between histamine H3KO mice and WT mice was observed. Following treatment with METH, the number of c-Fos–positive neurons in the the caudate-putamen of histamine H3KO mice was lower than that in the caudate-putamen of WT mice. In contrast, there was no significant difference in the number of the psychostimulant-induced c-Fos–positive cells in the nucleus accumbens between the two strains of mice. These findings suggest that deficiency in histamine H3 receptors may have inhibitory effects on psychostimulant-induced increase in locomotion, but insignificant effects on the reward.

Suppression of Histamine Signaling by Probiotic Lac-B: a Possible Mechanism of Its Anti-allergic Effect

It has been shown that probiotic bacteria are effective for the treatment of allergic diseases. As histamine plays a central role in allergic diseases, it is possible that probiotic bacteria affect the allergy-related histamine signaling. Here, we investigated the effect of Lac-B, a mixture of freeze-dried Bifidobacterium infantis and Bifidobacterium longum, on the allergy-related histamine signaling. In the nasal allergy model rats made by sensitization and provocation with toluene 2,4-diisocyanate (TDI) for 3 weeks, TDI provocation caused acute allergy–like behaviors along with significant up-regulation of histamine H1 receptor (H1R) and histidine decarboxylase (HDC) mRNA expression, increased HDC activity, histamine content, and [3H]mepyramine binding activity in nasal mucosa. Prolonged treatment with Lac-B (40 mg/rat, p.o.) significantly suppressed both the allergy-like behaviors and all of the above mentioned factors involved in histamine signaling. Our findings indicate that oral administration of Lac-B showed significant anti-allergic effect through suppression of both H1R and HDC gene expression followed by decrease in H1R, HDC protein level, and histamine content. Suppression of histamine signaling may be a novel target of probiotics in preventing allergic diseases.

Progress in Allergy Signal Research on Mast Cells: Up-Regulation of Histamine Signal-Related Gene Expression in Allergy Model Rats

Brown Norway allergy model rats sensitized to toluene 2,4-diisocyanate (TDI) were developed. Histamine H1receptor mRNA level was elevated in nasal mucosa of allergy model rats after the provocation with TDI, which was followed by H1-receptor up-regulation. Elevation of histamine H1receptor mRNA was partially suppressed by d-chlorpheniramine and olopatadine, antihistamines. Histamine induced increase in histamine H1receptor gene expression in vitro, and the protein kinase C-δ isoform was suggested to mediate the gene expression. On the other hand, elevation of histamine H1receptor mRNA was completely suppressed by dexamethasone in allergy model rats. Provocation with TDI also induced mRNA elevation of histidine decarboxylase, a sole histamine-forming enzyme, followed by the increase of both HDC activity and histamine content in nasal mucosa of allergy model rats. HDC mRNA elevation and increase in both HDC activity and histamine level were almost completely suppressed by dexamethasone. These observations suggest that histamine H1receptor up-regulation and increase in histamine level play an important role in allergy through the regulation of histamine signaling.

Stimulation of Histamine H1 Receptor Up-Regulates Histamine H1 Receptor Itself Through Activation of Receptor Gene Transcription

Histamine is a major mediator in allergy acting mainly through the histamine H1 receptor (H1R). Although H1R up-regulation has been suggested as an important step for induction of allergic symptoms, little is known about the regulation of H1R level. Here we report that the activation of H1R up-regulates H1R through augmentation of H1R mRNA expression in HeLa cells. Histamine stimulation significantly increased both H1R promoter activity and mRNA level without alteration in mRNA stability. H1R protein was also up-regulated by histamine. An H1R antagonist but not histamine H2 receptor antagonist blocked histamine-induced up-regulation of both promoter activity and mRNA expression. A protein kinase C (PKC) activator, phorbol-12-myristate-13-acetate, increased H1R mRNA expression, whereas an activator of PKA or PKG (8-Br-cAMP or 8-Br-cGMP, respectively) did not. Furthermore, histamine-induced upregulation of both promoter activity and mRNA level were completely suppressed by the PKC inhibitor Ro-31-8220. H1R antagonists have long been thought to block H1R and inhibit immediate allergy symptoms. In addition to this short-term effect, our data propose their long-term inhibitory effect against allergic diseases by suppressing PKC-mediated H1R gene transcription. This finding provides new insights into the therapeutic target of H1R antagonist in allergic diseases.

Enhanced antinociceptive effects of morphine in histamine H2 receptor gene knockout mice

We have previously shown that antinociceptive effects of morphine are enhanced in histamine H1 receptor gene knockout mice. In the present study, involvement of supraspinal histamine H2 receptor in antinociception by morphine was examined using histamine H2 receptor gene knockout (H 2KO) mice and histamine H 2 receptor antagonists. Antinociception was evaluated by assays for thermal (hot-plate, tail-flick and paw-withdrawal tests), mechanical (tail-pressure test) and chemical (formalin and capsaicin tests) stimuli. Thresholds for pain perception in H 2KO mice were higher than wild-type mice. Antinociceptive effects of intracerebroventricularly administered morphine were enhanced in the H 2KO mice compared to wild-type mice. Intracerebroventricular co-administration of morphine and cimetidine produced significant antinociceptive effects in the wild-type mice when compared to morphine or cimetidine alone. Furthermore, zolantidine, a selective and hydrophobic H2 receptor antagonist, enhanced the effects of morphine in all nociceptive assays examined. These results suggest that histamine exerts inhibitory effects on morphine-induced antinociception through H2 receptors at the supraspinal level. Our present and previous studies suggest that H1 and H2 receptors cooperatively function to modulate pain perception in the central nervous system.

Alternative Promoter Use and Splice Variation in the Human Histamine H1 Receptor Gene

Upstream gene structure and mRNA expression of the human histamine H1 receptor gene was investigated in cells relevant to the pathogenesis of asthma, (primary cultured human airway smooth muscle (HASM) cells, primary cultured human bronchial epithelial cells and bronchial epithelial cell line [BEAS2B]), and other tissues known to express histamine H1 receptors (placenta and brain). Splice variation of the 5' terminal exons gave three separate locations for novel promoters upstream of the detected transcription start sites. Further splice variants in the 5' untranslated region were also observed. Transient transfections of promoter/luciferase constructs showed these regions directed expression in HASM cells and BEAS2B cells. Polymorphism screening of the major regulatory regions identified a number of novel single-nucleotide polymorphisms. Expression of splice variants was confirmed by real-time PCR assays. Results showed one 5' terminal exon splice variant, comprising exons B/K, expressed preferentially in all tissues. Interestingly, the other 5' terminal exon splice variants showed tissue-specific patterns of expression, with variant F/K expressed negligibly (0.1%) in HASM cells, but accounting for 19.3% and 8.3% of total expression in BEAS2B cells and differentiated human bronchial epithelial cells, respectively. Splice variant A/K was second most highly expressed in differentiated human bronchial epithelial cells (23%), whereas its expression in BEAS2B and HASM cells was 1.7% and 4.4%, respectively. These data suggest the use of alternative promoters directing human H1 receptor gene expression, both within and between cell types.

Recent Advances in Molecular Pharmacology of the Histamine Systems: Regulation of Histamine H1 Receptor Signaling by Changing Its Expression Level

Histamine H1 receptor (H1R) signaling is regulated by changing its expression level. Two mechanisms are involved in this regulation. One is down-regulation through receptor desensitization. Receptor phosphorylation seemed crucial because stimulation of the mutant H1R lacking five putative phosphorylation sites did not show down-regulation. The phosphorylation level of the mutant receptor was much smaller than that of the wild type ones by several protein kinases. The other is up-regulation through activation of receptor gene expression. Protein kinase C (PKC) signaling was suggested to be involved in this up-regulation. Regulation of H1R expression level was mediated not only through H1R but also autonomic nerve receptors. Stimulation of M3 muscarinic receptors (M3R) induced both down-regulation and up-regulation of H1R. Down-regulation of M3R-mediated H1R seemed not to be mediated by PKC activation, although PKC activation induced H1R phosphorylation. Elevation of H1R expression was induced by the stimulation of M3Rs. PKC was suggested to be involved in this up-regulation. Stimulation of beta2-adrenergic receptors induced H1R down-regulation through several mechanisms. One of them is enhanced receptor degradation after desensitization and another is suppression of receptor synthesis that includes the suppression of receptor gene expression and enhanced degradation of the receptor mRNA. Protein kinase A was suggested to be involved in enhanced degradation and the activation of the receptor gene expression. Elevation of both H1R expression and its mRNA was observed in nasal mucosa of nasal hypersensitivity allergy model rat after toluene diisocyanate provocation. These results suggest that activation of H1R gene expression plays an important patho-physiological role in allergy. Elevation of the mRNA was partially but significantly suppressed by antihistamines.

Histamine H1 and H2 receptor gene and protein levels are differentially expressed in the hearts of rodents and humans.

Histamine is highly concentrated in the heart of animals and humans. Excessive release in pathophysiological conditions, such as immediate hypersensitivity and septic shock, causes cardiac dysfunction and arrhythmias. Previous pharmacological studies revealed that H(1) and H(2) receptors mediate these effects. Yet, an accurate estimate of the distribution and molecular characteristics of cardiac histamine receptors is missing. Recently, the genes encoding H(1) and H(2) receptors have been cloned, and the amino acid sequence and protein structure have been elucidated. Accordingly, we analyzed gene and protein expression levels of H(1) and H(2) receptors in atria and ventricles of guinea pig, rabbit, rat, and human hearts. With immunocytochemical techniques, we examined the regional expression of H(1) and H(2) receptor proteins in the sinoatrial and atrioventricular nodes and surrounding myocardium of the guinea pig heart. Northern and Western blot studies revealed that cardiac histamine H(1) and H(2) receptors are variably distributed among different mammalian species and different regions of the heart, whereas H(2) receptors are abundantly expressed in human atrial and ventricular myocardium. These findings agree with those of previous pharmacological studies, clearly demonstrating that the responses of the heart to histamine depend on the expression level of H(1) and H(2) receptors. The highly abundant expression of H(2) receptors in the human heart substantiates histamine arrhythmogenicity in various disease states. The new knowledge of a differential distribution of histamine receptor subtypes in the human heart will foster a better understanding of histamine roles in cardiovascular pathophysiology and may contribute to new therapeutic approaches to histamine-induced cardiac dysfunctions.

Increased brain histamine H3 receptor expression during hibernation in golden-mantled ground squirrels

BackgroundHibernation is a state of extremely reduced physiological functions and a deep depression of CNS activity. We have previously shown that the histamine levels increase in the brain during hibernation, as does the ratio between histamine and its first metabolite, suggesting increased histamine turnover during this state. The inhibitory histamine H3 receptor has both auto- and heteroreceptor function, rendering it the most likely histamine receptor to be involved in regulating the activity of histamine as well as other neurotransmitters during hibernation. In view of accumulating evidence that there is a global depression of transcription and translation during hibernation, of all but a few proteins that are important for this physiological condition, we reasoned that an increase in histamine H3 receptor expression would clearly indicate an important hibernation-related function for the receptor.ResultsIn 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. These results indicate that there is a hibernation-related increase in H3 receptor expression in cortical neurons and in striatopallidal and striatonigral GABAergic neurons. GTP-γ-S binding autoradiography shows that the H3 receptors in the globus pallidus and substantia nigra can be stimulated by histamine throughout the hibernation cycle, suggesting that they are functionally active during hibernation.ConclusionsThese results show that the histamine H3 receptor gene is one of the few with a transcript that increases during hibernation, indicating an important role for the receptor in regulating this state. Moreover, the receptor is functionally active in the basal ganglia, suggesting a function for it in regulating e.g. dopaminergic transmission during hibernation.

Identification of Bphs, an autoimmune disease locus, as histamine receptor H1.

Bphs controls Bordetella pertussis toxin (PTX)-induced vasoactive amine sensitization elicited by histamine (VAASH) and has an established role in autoimmunity. We report that congenic mapping links Bphs to the histamine H1 receptor gene (Hrh1/H1R) and that H1R differs at three amino acid residues in VAASH-susceptible and -resistant mice. Hrh1-/- mice are protected from VAASH, which can be restored by genetic complementation with a susceptible Bphs/Hrh1 allele, and experimental allergic encephalomyelitis and autoimmune orchitis due to immune deviation. Thus, natural alleles of Hrh1 control both the autoimmune T cell and vascular responses regulated by histamine after PTX sensitization.

Structure of the human histamine H3 receptor gene (HRH3) and identification of naturally occurring variations.

Neurotransmitter release is modulated by presynaptic histamine H(3) receptors located on histaminergic, noradrenergic and other nonhistaminergic neurons of the central and peripheral nervous system. 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. The coding region of the gene consists of three exons interrupted by two introns of approximately 1 kb in size. Exon boundaries only partly correspond to transmembrane domain organization. The homozygous Ala280Val variation in the third intracellular loop of the histamine H(3) receptor of a patient with Shy-Drager syndrome may be related to the etiology of the illness due to altered norepinephrine release. Furthermore, knowledge of the gene structure allows the verification of alternative splicing of the receptor. The corresponding histamine H(3) receptor isoforms as reported for the guinea pig and rat histamine H(3) receptor in different brain regions are not found in the human brain.

Arousal effect of orexin A depends on activation of the histaminergic system.

Orexin neurons are exclusively localized in the lateral hypothalamic area and project their fibers to the entire central nervous system, including the histaminergic tuberomammillary nucleus (TMN). Dysfunction of the orexin system results in the sleep disorder narcolepsy, but the role of orexin in physiological sleep-wake regulation and the mechanisms involved remain to be elucidated. Here we provide several lines of evidence that orexin A induces wakefulness by means of the TMN and histamine H(1) receptor (H1R). Perfusion of orexin A (5 and 25 pmol/min) for 1 hr into the TMN of rats through a microdialysis probe promptly increased wakefulness for 2 hr after starting the perfusion by 2.5- and 4-fold, respectively, concomitant with a reduction in rapid eye movement (REM) and non-REM sleep. Microdialysis studies showed that application of orexin A to the TMN increased histamine release from both the medial preoptic area and the frontal cortex by approximately 2-fold over the baseline for 80 to 160 min in a dose-dependent manner. Furthermore, infusion of orexin A (1.5 pmol/min) for 6 hr into the lateral ventricle of mice produced a significant increase in wakefulness during the 8 hr after starting infusion to the same level as the wakefulness observed during the active period in wild-type mice, but not at all in H1R gene knockout mice. These findings strongly indicate that the arousal effect of orexin A depends on the activation of histaminergic neurotransmission mediated by H1R.

Genomic organization and characterization of splice variants of the human histamine H3 receptor.

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. Using PCR, six alternative splice variants of the H3 receptor were cloned from human thalamus. These variants were found to be coexpressed in human brain, but their relative distribution varied in a region-specific manner. These isoforms displayed either a deletion in the putative second transmembrane domain (TM), H3(DeltaTM2, 431aa) or a variable deletion in the third intracellular loop (i3), H3(Deltai3, 415aa), H3(Deltai3, 365aa), H3(Deltai3, 329aa) and H3(DeltaTM5+Deltai3, 326aa). In order to determine the biological role of the H3 receptor variants compared with the 'original' H3(445aa) receptor, three isoforms, namely H3(445aa), H3(DeltaTM2, 431aa) and H3(Deltai3, 365aa), were expressed in CHO cells and their pharmacological properties were investigated. Binding studies showed that H3(DeltaTM2, 431aa) transiently expressed in CHO cells was unable to bind [125I]iodoproxyfan, whereas both the H3(445aa) and H3(Deltai3, 365aa) receptors displayed a high affinity for [125I]iodoproxyfan [K(d)=28+/-5 pM (n=4) and 8+/-1 pM (n=5) respectively]. In addition, H3(Deltai3, 365aa) possessed the same pharmacological profile as the H3(445aa) receptor. However, in CHO cells expressing H3(Deltai3, 365aa), H3 agonists did not inhibit forskolin-induced cAMP production, stimulate [35S]guanosine 5'-[gamma-thio]triphosphate ([35S]GTP[S]) binding or stimulate intracellular Ca(2+) mobilization. Therefore the 80-amino-acid sequence located at the C-terminal portion of i3 plays an essential role in H3 agonist-mediated signal transduction. The existence of multiple H3 isoforms with different signal transduction capabilities suggests that H3-mediated biological functions might be tightly regulated through alternative splicing mechanisms.

Genomic organization and characterization of splice variants of the human histamine H3 receptor

In the present paper we report the genomic organization of the human histamine H3-receptor gene, which consists of four exons spanning 5.5kb on chromosome 20. Using PCR, six alternative splice variants of the H3 receptor were cloned from human thalamus. These variants were found to be coexpressed in human brain, but their relative distribution varied in a region-specific manner. These isoforms displayed either a deletion in the putative second transmembrane domain (TM), H3(∆TM2, 431aa) or a variable deletion in the third intracellular loop (i3), H3(∆i3, 415aa), H3(∆i3, 365aa), H3(∆i3, 329aa) and H3(∆TM5+∆i3, 326aa). In order to determine the biological role of the H3 receptor variants compared with the ‘original’ H3(445aa) receptor, three isoforms, namely H3(445aa), H3(∆TM2, 431aa) and H3(∆i3, 365aa), were expressed in CHO cells and their pharmacological properties were investigated. Binding studies showed that H3(∆TM2,431aa) transiently expressed in CHO cells was unable to bind [125I]iodoproxyfan, whereas both the H3(445aa) and H3(∆i3, 365aa) receptors displayed a high affinity for [125I]iodoproxyfan [Kd = 28±5pM (n = 4) and 8±1pM (n = 5) respectively]. In addition, H3(∆i3, 365aa) possessed the same pharmacological profile as the H3(445aa) receptor. However, in CHO cells expressing H3(∆i3, 365aa), H3 agonists did not inhibit forskolin-induced cAMP production, stimulate [35S]guanosine 5′-[γ-thio]triphosphate ([35S]GTP[S]) binding or stimulate intracellular Ca2+ mobilization. Therefore the 80-amino-acid sequence located at the C-terminal portion of i3 plays an essential role in H3 agonist-mediated signal transduction. The existence of multiple H3 isoforms with different signal transduction capabilities suggests that H3-mediated biological functions might be tightly regulated through alternative splicing mechanisms.

Chromosomal mapping and organization of the human histamine H3 receptor gene.

The histamine H3 receptor (H3R) was recently cloned, and two isoforms, termed H3L and H3S, differing in the third intracytosolic loop, were isolated but the chromosomal mapping and organization of its gene remained unknown. PCR analysis of a human x rodent cell hybrid panel indicated that the H3R gene is located in the telomeric region of chromosome 20q. Alignment of human H3R cDNA sequences with DNA sequences of this chromosome revealed that its coding region comprises three exons interrupted by two introns located in the second transmembrane domain (TM2) and second intracytosolic loop, respectively. Thus the organization of the H3R gene indicates that the H3L and H3S isoforms, that we characterized not only in rodents but also in humans, are generated by retention and deletion, respectively, of a pseudo-intron located in the third intracytosolic loop.

Human histamine H2 receptor gene: multiple transcription initiation and tissue-specific expression

We have characterized the genomic structure of 12.3 kb of the 5′-flanking region of the human histamine H2 receptor gene. The multiple transcription initiation sites of the human histamine H2 receptor gene were mapped utilizing the 5′-end cap structure of mRNA. We found that a 85 bp segment (−610–−525 bp) immediately upstream of the initiation site exhibits a strong promoter activity in the gastric adenocarcinoma, MNK45, expressing human histamine H2 receptor. A 4.8 kb transcript of the human histamine H2 receptor gene was found in the placenta, spinal cord, lymph node and bone marrow in addition to the previously reported tissues including the heart, brain and stomach, whereas a 1.8 kb transcript was observed in almost all tissues examined. 3′-rapid amplification of cDNA ends revealed the corresponding length of the 3′-untranslated region. These results suggest that the 3′-untranslated region may be involved in the differential expression.

Identification of the histamine H1 receptor gene as a differentially repressed target of the human TR2 orphan receptor.

We have identified a DNA response element (TR2RE-HR) in the 3' flanking region of the human histamine H1 receptor gene as a target for the TR2 orphan receptor, a member of the steroid/thyroid hormone receptor superfamily. The application of both tetracycline inducible and improved differential display systems has allowed us to isolate a cDNA fragment differentially regulated by the expression of the TR2 orphan receptor. Northern blot and sequencing analysis demonstrated that the expression of the human histamine H1 receptor gene was differentially repressed by the TR2 orphan receptor. Electrophoretic mobility shift assay further revealed a specific binding (dissociation constant = 26.2 nM) between the TR2 orphan receptor and the wildtype TR2RE-HR, but not the mutant TR2RE-HR. In addition, reporter gene expression assay indicated that the TR2 orphan receptor may suppress the expression of luciferase activities in a dose-dependent manner via the TR2RE-HR in HeLa cells. Our results demonstrate that the histamine H1 receptor gene could represent one of the target genes directly regulated by the human TR2 orphan receptor.

Desensitization of the histamine H1-receptor and transcriptional down-regulation of histamine H1-receptor gene expression in bovine tracheal smooth muscle.

We have investigated the role of protein kinase C (PKC) in the desensitization of histamine H1-receptors and in the expression of the histamine H1-receptor gene in airway smooth muscle. Prolonged 4beta-phorbol 12,13 dibutyrate (PDBu) pretreatment (4 h, 100 nM-1 microM) of bovine trachealis caused a concentration-dependent loss of contraction in response to histamine H1-receptor stimulation, which was associated with a concentration-dependent decrease in histamine-induced total [3H]-inositol phosphates accumulation. In contrast, the responses to sodium fluoride, a direct G-protein activator, were unalterd by PDBu (100-300 nM) pre-incubation and only slightly reduced following incubation with 1 microM PDBu. A selective PKC inhibitor, GF 109203X, partially blocked the PDBu (1 microM)-induced desensitization and completely blocked the effect of 100 nM PDBu, confirming the involvement of PKC. Binding experiments using [3H]-pyrilamine revealed a class of high-affinity binding sites within the range for the histamine H1 receptor in airway smooth muscle. PDBu (1 microM) pretreatment for 4 h did not change the number of histamine H1 receptors. PDBu (1 microM) exposure caused a time-dependent reduction in the steady-state levels of histamine H1-receptor mRNA, which was inhibited by pre-incubation with GF 109203X and by cycloheximide, a protein synthesis inhibitor. Nuclear run-on assays revealed a 50% reduction in the rate of histamine H1-receptor gene transcription after 17 h PDBu pretreatment, whereas mRNA stability was not affected by PDBu pretreatment (17 h). In conclusion, we have shown a PKC-mediated desensitization of the histamine H1-receptor in BTSM and a transcriptional down-regulation of the histamine H1-receptor gene expression, which requires new protein synthesis.

Structure of the human histamine H1 receptor gene.

Histamine H1 receptor expression has been reported to change in disorders such as allergic rhinitis, autoimmune myocarditis, rheumatoid arthritis and atherosclerosis. Here we report the isolation and characterization of genomic clones containing the 5' flanking (regulatory) region of the human histamine H1 receptor gene. An intron of approx. 5.8 kb was identified in the 5' untranslated region, which suggests that an entire subfamily of G-protein-coupled receptors may contain an intron immediately upstream of the start codon. The transcription initiation site was mapped by 5' rapid amplification of cDNA ends to a region 6.2 kb upstream of the start codon. 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. The promoter sequence shares a number of characteristics with the promoter sequences of other G-protein-coupled receptor encoding genes, including binding sites for several transcription factors, and the absence of TATA and CAAT sequences at the appropriate locations. The promoter sequence described here differs from that reported previously [Fukui, Fujimoto, Mizuguchi, Sakamoto, Horio, Takai, Yamada and Ito (1994) Biochem. Biophys. Res. Commun. 201, 894-901] because the reported genomic clone was chimaeric. Furthermore our study provides evidence that the 3' untranslated region of the H1 receptor mRNA is much longer than previously accepted. Together, these findings provide a complete view of the structure of the human histamine H1 receptor gene. Both the coding region of the H1 receptor gene and its promoter region were independently mapped to chromosome 3p25.

Characterization of histamine H1 receptor gene knocked-out mice

Characterization of histamine H1 receptor gene knocked-out mice