共查询到20条相似文献,搜索用时 15 毫秒
1.
Nakamura T Itadani H Hidaka Y Ohta M Tanaka K 《Biochemical and biophysical research communications》2000,279(2):615-620
A new histamine receptor, HH4R, was cloned from human leukocyte cDNA. The deduced amino acid sequence showed about 40% identity to that of the human histamine H3 receptor, HH3R. HH4R-expressing cells responded to histamine, inhibiting forskolin-induced cAMP accumulation. An H3 agonist, N-alpha-methylhistamine (NAMHA), bound specifically to HH4R, while another H3 agonist, R(-)-alpha-methylhistamine (RAMHA), and the H3 antagonist, thioperamide, competed with this binding. RAMHA, NAMHA, and imetit inhibited forskolin-induced cAMP accumulation in HH4R-expressing cells. However, the binding affinities and agonistic activities of H3 agonists to HH4R were weaker than those to HH3R. 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. These observations indicate that the clone is a distinct histamine receptor from HH3R, and thus is named HH4R. 相似文献
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A cDNA clone of rat uterus estrogen receptor (ER) has been isolated and sequenced. This clone contains a complete open reading frame encoding 600 amino acid residues which is 5 and 11 amino acids larger than the corresponding molecules of human and chicken, respectively. The molecular weight of this protein is calculated to be 67,029. When this clone was ligated to the pSV2 vector and transfected into COS7 cells, a protein was produced that had the same affinity to estrogen as rat uterus ER. This sequence shows 88% homology with human ER; 528 amino acids are identical and 14 amino acids are conservative substitutions. The comparison of rat, human and chicken ER sequences indicate the presence of three highly conserved regions suggesting that these regions play important roles in ER function. The putative DNA-binding domain is completely identical in rat, human and chicken. The C-terminal half region which is thought to be the estrogen binding domain is also highly conserved and is rich in hydrophobic amino acid residues. Southern blot analysis of genomic DNA with ER cDNA as a probe has shown that related sequences are present in the genome. 相似文献
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I Gantz G Munzert T Tashiro M Sch?ffer L Wang J DelValle T Yamada 《Biochemical and biophysical research communications》1991,178(3):1386-1392
We utilized the technique of polymerase chain reaction with oligonucleotide primers based upon the nucleotide sequence of the canine H2 histamine receptor gene which we recently isolated to clone its human homologue. Transfection of a construct of this gene in Colo-320 DM cells led to the expression of a receptor that bound to [methyl-3H] tiotidine and was linked to 3',5'cyclic adenosine monophosphate (cAMP) generation in response to histamine. Both cAMP generation and [methyl-3H] tiotidine binding were inhibited with the H2 histamine receptor selective antagonist cimetidine but not diphenhydramine or thioperamide which are, respectively, H1 and H3 histamine receptor antagonists. These data confirm that we have successfully cloned a novel gene encoding the human H2 histamine receptor. 相似文献
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Savall BM Gomez L Chavez F Curtis M Meduna SP Kearney A Dunford P Cowden J Thurmond RL Grice C Edwards JP 《Bioorganic & medicinal chemistry letters》2011,21(21):6577-6581
This report discloses the development of a series of tricyclic histamine H(4) receptor antagonists. Starting with a low nanomolar benzofuranopyrimidine HTS hit devoid of pharmaceutically acceptable properties, we navigated issues with metabolism and solubility to furnish a potent, stable and water soluble tricyclic histamine H(4) receptor antagonist with desirable physiochemical parameters which demonstrated efficacy a mouse ova model. 相似文献
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Piletz JE Ivanov TR Sharp JD Ernsberger P Chang CH Pickard RT Gold G Roth B Zhu H Jones JC Baldwin J Reis DJ 《DNA and cell biology》2000,19(6):319-329
The imidazoline-1 receptor (IR1) is considered a novel target for drug discovery. Toward cloning an IR1, a truncated cDNA clone was isolated from a human hippocampal lambda gt11 cDNA expression library by relying on the selectivity of two antisera directed against candidate IR proteins. Amplification reactions were performed to extend the 5' and 3' ends of this cDNA, followed by end-to-end PCR and conventional cloning. The resultant 5131-basepair molecule, designated imidazoline receptor-antisera-selected (IRAS) cDNA, was shown to encode a 1504-amino acid protein (IRAS-1). No relation exists between the amino acid sequence of IRAS-1 and proteins known to bind imidazolines (e.g., it is not an alpha2-adrenoceptor or monoamine oxidase subtype). However, certain sequences within IRAS-1 are consistent with signaling motifs found in cytokine receptors, as previously suggested for an IR1. An acidic region in IRAS-1 having an amino acid sequence nearly identical to that of ryanodine receptors led to the demonstration that ruthenium red, a dye that binds the acidic region in ryanodine receptors, also stained IRAS-1 as a 167-kD band on SDS gels and inhibited radioligand binding of native I1 sites in untransfected PC-12 cells (a source of authentic I1 binding sites). Two epitope-selective antisera were also generated against IRAS-1, and both reacted with the same 167-kD band on Western blots. In a host-cell-specific manner, transfection of IRAS cDNA into Chinese hamster ovary cells led to high-affinity I1 binding sites by criteria of nanomolar affinity for moxonidine and rilmenidine. Thus, IRAS-1 is the first protein discovered with characteristics of an IR1. 相似文献
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Kerstin Sander Tim Kottke Yusuf Tanrikulu Ewgenij Proschak Lilia Weizel Erich H. Schneider Roland Seifert Gisbert Schneider Holger Stark 《Bioorganic & medicinal chemistry》2009,17(20):7186-7196
The human histamine H4 receptor (hH4R) is a promising new target in the therapy of inflammatory diseases and disorders of the immune system. For the development of new H4R antagonists a broad ligand-based virtual screening was performed resulting in two hits. The dissection of their common annelated aromatic core into its heteromonocyclic components showed that 2,4-diaminopyrimidine is a potent hH4R affinity scaffold, which was comprehensively investigated. Structure–activity relationship studies revealed that slight structural changes evoke extensive differences in functional activities and potencies: while o- and p-substituted benzyl amines mainly showed partial agonism, m-substituted and rigidified ones exhibited inverse agonist efficacy. 相似文献
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Cloning and characterization of dominant negative splice variants of the human histamine H4 receptor
van Rijn RM van Marle A Chazot PL Langemeijer E Qin Y Shenton FC Lim HD Zuiderveld OP Sansuk K Dy M Smit MJ Tensen CP Bakker RA Leurs R 《The Biochemical journal》2008,414(1):121-131
The H(4)R (histamine H(4) receptor) is the latest identified member of the histamine receptor subfamily of GPCRs (G-protein-coupled receptors) with potential functional implications in inflammatory diseases and cancer. The H(4)R is primarily expressed in eosinophils and mast cells and has the highest homology with the H(3)R. The occurrence of at least twenty different hH(3)R (human H(3)R) isoforms led us to investigate the possible existence of H(4)R splice variants. In the present paper, we report on the cloning of the first two alternatively spliced H(4)R isoforms from CD34+ cord blood-cell-derived eosinophils and mast cells. These H(4)R splice variants are localized predominantly intracellularly when expressed recombinantly in mammalian cells. We failed to detect any ligand binding, H(4)R-ligand induced signalling or constitutive activity for these H(4)R splice variants. However, when co-expressed with full-length H(4)R [H(4)R((390)) (H(4)R isoform of 390 amino acids)], the H(4)R splice variants have a dominant negative effect on the surface expression of H(4)R((390)). We detected H(4)R((390))-H(4)R splice variant hetero-oligomers by employing both biochemical (immunoprecipitation and cell-surface labelling) and biophysical [time-resolved FRET (fluorescence resonance energy transfer)] techniques. mRNAs encoding the H(4)R splice variants were detected in various cell types and expressed at similar levels to the full-length H(4)R((390)) mRNA in, for example, pre-monocytes. We conclude that the H(4)R splice variants described here have a dominant negative effect on H(4)R((390)) functionality, as they are able to retain H(4)R((390)) intracellularly and inactivate a population of H(4)R((390)), presumably via hetero-oligomerization. 相似文献
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Lane CA Hay D Mowbray CE Paradowski M Selby MD Swain NA Williams DH 《Bioorganic & medicinal chemistry letters》2012,22(2):1156-1159
This letter describes the discovery and synthesis of a series of octahydropyrrolo[3,4-c]pyrrole based selective histamine hH4 receptor antagonists. The amidine compound 20 was found to be a potent and selective histamine H4 receptor antagonist with moderate clearance and a high volume of distribution. 相似文献
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《Gene》1997,195(2):337-339
Interleukin-15 (IL-15) is a recently identified growth and differentiation factor with an important potential role in the initial immune responses to infection. To enable the study of the role of this cytokine in the protective immune-mechanisms generated against parasitic diseases of swine, cDNA was generated from a macrophage enriched adherent cell population from peripheral blood mononuclear cells (PBMC). This cDNA was used for the enzymatic amplification of the porcine IL-15 sequence using human IL-15-derived primers. The open-reading frame of the porcine IL-15 cDNA is 486 base pairs (bp) in length and encodes a 162-amino-acid (aa) protein. Comparisons of the predicted swine protein sequence with those predicted from human, bovine and mouse IL-15 sequences indicate similarities of 82.1, 84.6, and 71.6%, respectively. 相似文献
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cDNA cloning and characterization of vinculin mRNA 总被引:5,自引:0,他引:5
M D Coutu D J Simon A E Brown S W Craig 《Biochemical and biophysical research communications》1987,147(2):637-643
Vinculin and meta-vinculin are related proteins that localize to adherens junctions. To facilitate studies on the biology of these proteins cDNA clones were isolated from a chick embryonic library made in lambda gt 11. Three clones, accounting for 1/2 of the vinculin message, were identified by immunological analyses of fusion proteins and by hybrid-arrested translation. Sequence analyses of the 3' ends of these clones reveal allelic variants. Northern blot analyses suggests the presence of multiple vinculin messages, the most prominent one at 6.2 kb, almost twice the size needed to encode vinculin. 相似文献
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Kamohara M Takasaki J Matsumoto M Saito T Ohishi T Ishii H Furuichi K 《The Journal of biological chemistry》2000,275(35):27000-27004
Leukotriene B(4) is a potent lipid mediator known to be implicated mainly in inflammatory actions. Previous pharmacological studies indicated the existence of only one class of G protein-coupled receptor for leukotriene B(4), for which a candidate gene, namely BLT, had been identified. Here we report the isolation of another gene encoding a functional G protein-coupled receptor for leukotriene B(4), named JULF2. JULF2 is a novel G protein-coupled receptor of 358 amino acids that shares 36.6% amino acid identity with human BLT. According to genomic information, the JULF2 gene is located on the chromosome 14, about 4 kilobases upstream of the BLT gene. During screening of endogenous ligands for JULF2, we found that leukotriene B(4) induced inhibition of forskolin-stimulated cAMP accumulation in Chinese hamster ovary cells, stably expressing JULF2. Additionally, Chinese hamster ovary cells expressing exogenous JULF2 showed chemotactic responses with leukotriene B(4) in a pertussis toxin-sensitive manner. A large amount of JULF2 mRNA was detected in the human spleen and the peripheral blood leukocytes. Furthermore, JULF2 mRNA was expressed in mononuclear lymphocytes, in which BLT mRNA was barely detected. The discovery of this second leukotriene B(4) receptor will eventually lead to a better understanding of the classification of leukotriene B(4) receptors and reconsideration of the pathophysiological role of leukotriene B(4). 相似文献
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Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes 总被引:14,自引:0,他引:14
Oda T Morikawa N Saito Y Masuho Y Matsumoto S 《The Journal of biological chemistry》2000,275(47):36781-36786
Recently cDNA encoding the histamine H3 receptor was isolated after 15 years of considerable research. However, several studies have proposed heterogeneity of the H3 receptor. We report here the molecular cloning and characterization of a novel type of histamine receptor. A novel orphan G-protein-coupled receptor named GPRv53 was obtained through a search of the human genomic DNA data base and analyzed by rapid amplification of cDNA ends (RACE). GPRv53 possessed the features of biologic amine receptors and had the highest homology with H3 receptor among known G-protein-coupled receptors. Mammalian cells expressing GPRv53 were demonstrated to bind and respond to histamine in a concentration-dependent manner. In functional assays, not only an H3 receptor agonist, R-(alpha)-methylhistamine, but also a H3 receptor antagonist, clobenpropit, and a neuroleptic, clozapine, activated GPRv53-expressing cells. Tissue distribution analysis revealed that expression of GPRv53 is localized in the peripheral blood leukocytes, spleen, thymus, and colon, which was totally different from the H3 receptor, whose expression was restricted to the brain. The discovery of the GPRv53 receptor will open a new phase of research on the physiological role of histamine. 相似文献
15.
The nucleotide sequence data reported in this paper have been submitted to the GenBank sequence database and have been assigned the accession number L33910 相似文献
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Molecular cloning and characterization of horse DQA cDNA 总被引:1,自引:0,他引:1
The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number L33909 相似文献