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Pesquisa : D27.505.519.625.375.400 [Categoria DeCS]
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[PMID]:28888822
[Au] Autor:Ledneczki I; Tapolcsányi P; Gábor E; Éles J; Greiner I; Schmidt É; Némethy Z; Kedves RS; Balázs O; Román V; Lévay G; Mahó S
[Ad] Endereço:Chemical Works of Gedeon Richter Plc, H-1475, Budapest P.O. Box 27, Hungary. Electronic address: ledneczki@richter.hu.
[Ti] Título:Discovery of novel steroidal histamine H receptor antagonists/inverse agonists.
[So] Source:Bioorg Med Chem Lett;27(19):4525-4530, 2017 10 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Emerging from an HTS campaign, novel steroid-based histamine H receptor antagonists were identified and characterized. Structural moieties of the hit compounds were combined to improve binding affinities which resulted in compound 4 as lead molecule. During the lead optimization due to the versatile modifications of diamino steroid derivatives, several in vitro potent compounds with subnanomolar binding affinities to histamine H receptors were found. The unfavorable binding to rat muscarinic receptors was successfully reduced by tuning the basicity. Compound 20 showed significant in vivo activity in the rat dipsogenia model and could serve as a pharmacological tool in the future.
[Mh] Termos MeSH primário: Descoberta de Drogas
Agonistas dos Receptores Histamínicos/farmacologia
Antagonistas dos Receptores Histamínicos H3/farmacologia
Receptores Histamínicos H3/metabolismo
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Agonistas dos Receptores Histamínicos/síntese química
Agonistas dos Receptores Histamínicos/química
Antagonistas dos Receptores Histamínicos H3/síntese química
Antagonistas dos Receptores Histamínicos H3/química
Seres Humanos
Estrutura Molecular
Ratos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histamine Agonists); 0 (Histamine H3 Antagonists); 0 (Receptors, Histamine H3)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170911
[St] Status:MEDLINE


  2 / 1225 MEDLINE  
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[PMID]:28818391
[Au] Autor:Bertlich M; Ihler F; Weiss BG; Freytag S; Strupp M; Jakob M; Canis M
[Ad] Endereço:Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany. Electronic address: Mattis.Bertlich@med.uni-goettingen.de.
[Ti] Título:Role of capillary pericytes and precapillary arterioles in the vascular mechanism of betahistine in a guinea pig inner ear model.
[So] Source:Life Sci;187:17-21, 2017 Oct 15.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Betahistine is a histamine analogue that is used for the treatment of Menière's disease. Animal studies showed that it increases local blood flow in the stria vascularis. In terms of its mode of action, recent studies have prompted discussion of whether betahistine actively affects cochlear microcirculation by dilations of pericytes or of precapillary arterioles or by mere downstream effects. Hence, we investigated the effects of betahistine on cochlear capillary pericytes and precapillary arterioles. MAIN METHODS: The stria vascularis was visualized in 12 guinea pigs by in vivo fluorescence microscopy. In these, 152 pericytes were stained and local diameter at sites of pericyte somas and downstream controls as well as intravascular blood flow were measured before and after betahistine application. Moreover, in two guinea pigs the precapillary arterioles were visualized by 2-photon-microscopy before and after betahistine application. KEY FINDINGS: There was no significant change in capillary diameter at sites of pericyte somas after betahistine application compared to controls, baseline or downstream controls, even though cochlear blood flow increased significantly. The two-photon measurements indicated an active dilation of precapillary arterioles. SIGNIFICANCE: Since we found no evidence that betahistine affects cochlear microcirculation by cochlear pericytes, its main mode of action is evidently active dilation of pre-capillary arterioles. These findings are in line with similar effects reported in the central nervous system and indicate an active effect on cochlear microcirculation.
[Mh] Termos MeSH primário: Arteríolas/efeitos dos fármacos
beta-Histina/farmacologia
Orelha Interna/efeitos dos fármacos
Pericitos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Arteríolas/fisiologia
Orelha Interna/irrigação sanguínea
Cobaias
Agonistas dos Receptores Histamínicos/farmacologia
Microscopia de Fluorescência
Microscopia de Fluorescência por Excitação Multifotônica
Pericitos/fisiologia
Vasodilatadores/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histamine Agonists); 0 (Vasodilator Agents); X32KK4201D (Betahistine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170819
[St] Status:MEDLINE


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[PMID]:28688766
[Au] Autor:Shteinikov VY; Korosteleva AS; Tikhonova TB; Potapieva NN; Tikhonov DB
[Ad] Endereço:I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg, Russia.
[Ti] Título:Ligands of histamine receptors modulate acid-sensing ion channels.
[So] Source:Biochem Biophys Res Commun;490(4):1314-1318, 2017 Sep 02.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recently we found that synthetic compounds containing amino group linked to hydrophobic or aromatic moiety are potent modulators of the proton-gated channels (ASICs). These structures have clear similarity with ligands of histamine receptors. We have also demonstrated that histamine potentiates homomeric ASIC1a by shifting its activation dependence to less acidic conditions. In the present work the action of a series of histamine receptors ligands on recombinant ASIC1a and ASIC2a was characterized. Two types of action were found for ASIC1a. 1-methylhistamine, N-alpha-methylhistamine, dimaprit and thioperamide caused significant potentiation, which was pH-dependent and voltage-independent. The H4R antagonist A943931 caused inhibition, which is likely due to voltage-dependent pore block. ASIC2a were virtually insensitive to the drugs tested. We conclude that ligands of histamine receptors should also be considered as ASIC modulators.
[Mh] Termos MeSH primário: Canais Iônicos Sensíveis a Ácido/genética
Agonistas dos Receptores Histamínicos/farmacologia
Antagonistas dos Receptores Histamínicos/farmacologia
Histamina/farmacologia
Receptores Histamínicos/genética
[Mh] Termos MeSH secundário: Canais Iônicos Sensíveis a Ácido/metabolismo
Animais
Células CHO
Cricetulus
Dimaprit/farmacologia
Regulação da Expressão Gênica
Seres Humanos
Concentração de Íons de Hidrogênio
Ligantes
Metilistaminas/farmacologia
Técnicas de Patch-Clamp
Piperidinas/farmacologia
Receptores Histamínicos/metabolismo
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ASIC1 protein, human); 0 (ASIC2 protein, human); 0 (Acid Sensing Ion Channels); 0 (Histamine Agonists); 0 (Histamine Antagonists); 0 (Ligands); 0 (Methylhistamines); 0 (Piperidines); 0 (Receptors, Histamine); 0 (Recombinant Proteins); 6986-90-9 (alpha-methylhistamine); 820484N8I3 (Histamine); II4319BWUI (thioperamide); KCB81T4EOF (tele-methylhistamine); ZZQ699148P (Dimaprit)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170710
[St] Status:MEDLINE


  4 / 1225 MEDLINE  
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[PMID]:28526411
[Au] Autor:Iida T; Yoshikawa T; Kárpáti A; Matsuzawa T; Kitano H; Mogi A; Harada R; Naganuma F; Nakamura T; Yanai K
[Ad] Endereço:Department of Pharmacology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
[Ti] Título:JNJ10181457, a histamine H3 receptor inverse agonist, regulates in vivo microglial functions and improves depression-like behaviours in mice.
[So] Source:Biochem Biophys Res Commun;488(3):534-540, 2017 Jul 01.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Brain histamine acts as a neurotransmitter and regulates various physiological functions, such as learning and memory, sleep-wake cycles, and appetite regulation. We have recently shown that histamine H3 receptor (H3R) is expressed in primary mouse microglia and has a strong influence on critical functions in microglia, including chemotaxis, phagocytosis, and cytokine secretion in vitro. However, the importance of H3R in microglial activity in vivo remains unknown. Here, we examined the effects of JNJ10181457 (JNJ), a selective and potent H3R inverse agonist, on microglial functions ex vivo and in vivo. First, we injected ATP, which is a typical chemoattractant, into hippocampal slices to investigate the effect of JNJ on chemotaxis. ATP-induced microglial migration toward the injected site was significantly suppressed by JNJ treatment. Next, we examined whether JNJ affected microglial phagocytosis in hippocampal slices and in the prefrontal cortex. Microglial engulfment of dead neurons induced by N-methyl- -aspartate was inhibited in the presence of JNJ. The increase in zymosan particle uptake by activated microglia in the prefrontal cortex was prevented by JNJ administration. Finally, we determined the importance of JNJ in a lipopolysaccharide (LPS)-induced depression model. JNJ reduced the LPS-induced upregulation of microglial pro-inflammatory cytokines and improved depression-like behaviour in the tail-suspension test. These results demonstrate the inhibitory effects of JNJ on chemotaxis, phagocytosis, and cytokine production in microglia inside the brain, and highlight the importance of microglial H3R for brain homeostasis.
[Mh] Termos MeSH primário: Depressão/tratamento farmacológico
Agonistas dos Receptores Histamínicos/farmacologia
Microglia/efeitos dos fármacos
Morfolinas/farmacologia
Piperidinas/farmacologia
Receptores Histamínicos H3/metabolismo
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Camundongos
Microglia/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-(3-(4-piperidin-1-ylbut-1-ynyl)benzyl)morpholine); 0 (Histamine Agonists); 0 (Morpholines); 0 (Piperidines); 0 (Receptors, Histamine H3)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170521
[St] Status:MEDLINE


  5 / 1225 MEDLINE  
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[PMID]:28188663
[Au] Autor:Cilz NI; Lei S
[Ad] Endereço:Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota.
[Ti] Título:Histamine facilitates GABAergic transmission in the rat entorhinal cortex: Roles of H and H receptors, Na -permeable cation channels, and inward rectifier K channels.
[So] Source:Hippocampus;27(5):613-631, 2017 May.
[Is] ISSN:1098-1063
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the brain, histamine (HA) serves as a neuromodulator and a neurotransmitter released from the tuberomammillary nucleus (TMN). HA is involved in wakefulness, thermoregulation, energy homeostasis, nociception, and learning and memory. The medial entorhinal cortex (MEC) receives inputs from the TMN and expresses HA receptors (H , H , and H ). We investigated the effects of HA on GABAergic transmission in the MEC and found that HA significantly increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) with an EC of 1.3 µM, but failed to significantly alter sIPSC amplitude. HA-induced increases in sIPSC frequency were sensitive to tetrodotoxin (TTX), required extracellular Ca , and persisted when GDP-ß-S, a G-protein inactivator, was applied postsynaptically via the recording pipettes, indicating that HA increased GABA release by facilitating the excitability of GABAergic interneurons in the MEC. Recordings from local MEC interneurons revealed that HA significantly increased their excitability as determined by membrane depolarization, generation of an inward current at -65 mV, and augmentation of action potential firing frequency. Both H and H receptors were involved in HA-induced increases in sIPSCs and interneuron excitability. Immunohistochemical staining showed that both H and H receptors are expressed on GABAergic interneurons in the MEC. HA-induced depolarization of interneurons involved a mixed ionic mechanism including activation of a Na -permeable cation channel and inhibition of a cesium-sensitive inward rectifier K channel, although HA also inhibited the delayed rectifier K channels. Our results may provide a cellular mechanism, at least partially, to explain the roles of HA in the brain. © 2017 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Córtex Entorrinal/metabolismo
Histamina/metabolismo
Interneurônios/metabolismo
Transmissão Sináptica/fisiologia
Ácido gama-Aminobutírico/metabolismo
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Potenciais de Ação/fisiologia
Animais
Cálcio/metabolismo
Cátions/metabolismo
Césio/metabolismo
Córtex Entorrinal/citologia
Córtex Entorrinal/efeitos dos fármacos
Agonistas dos Receptores Histamínicos/farmacologia
Antagonistas dos Receptores Histamínicos/farmacologia
Interneurônios/citologia
Interneurônios/efeitos dos fármacos
Canais de Potássio Corretores do Fluxo de Internalização/metabolismo
Ratos Sprague-Dawley
Receptores de GABA-A/metabolismo
Receptores Histamínicos H1/metabolismo
Receptores Histamínicos H2/metabolismo
Receptores Histamínicos H3/metabolismo
Bloqueadores dos Canais de Sódio/farmacologia
Canais de Sódio/metabolismo
Transmissão Sináptica/efeitos dos fármacos
Técnicas de Cultura de Tecidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cations); 0 (Histamine Agonists); 0 (Histamine Antagonists); 0 (Potassium Channels, Inwardly Rectifying); 0 (Receptors, GABA-A); 0 (Receptors, Histamine H1); 0 (Receptors, Histamine H2); 0 (Receptors, Histamine H3); 0 (Sodium Channel Blockers); 0 (Sodium Channels); 1KSV9V4Y4I (Cesium); 56-12-2 (gamma-Aminobutyric Acid); 820484N8I3 (Histamine); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170425
[Lr] Data última revisão:
170425
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170212
[St] Status:MEDLINE
[do] DOI:10.1002/hipo.22718


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[PMID]:28178593
[Au] Autor:Wolak M; Bojanowska E; Staszewska T; Ciosek J; Juszczak M; Drobnik J
[Ad] Endereço:Department of Behavioral Pathophysiology, Chair of General and Experimental Pathology Medical University of Lodz, Lódz, Poland.
[Ti] Título:The role of histamine in the regulation of the viability, proliferation and transforming growth factor ß1 secretion of rat wound fibroblasts.
[So] Source:Pharmacol Rep;69(2):314-321, 2017 Apr.
[Is] ISSN:1734-1140
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Inflammation mediators play a regulatory role in repair processes. The study will examine the influence of histamine on wound fibroblast metabolic activity, viability, proliferation, and TGFß1 secretion. The study also will identify the histamine receptor involved in regulation of the tested repair processes. METHODS: Fibroblasts were obtained from the granulation tissue of wounds or intact dermis of rats. The MTT and BrdU assays were used to examine the effect of histamine (10 M-10 M) on the viability and metabolic activity of fibroblasts, and on their proliferative capacity. The influence of histamine receptor antagonists (i.e., ketotifen, ranitidine, ciproxifan and JNJ7777120) and agonists (2-pyridylethlamine dihydrochloride, amthamine dihydrobromide) was also investigated. The TGFß1 and histamine receptors H1 were evaluated by enzyme-linked immunosorbent assay. RESULTS: Histamine significantly increased granulation tissue fibroblast viability and metabolic activity at 10 and 10 M but did not change their proliferative activity. Only the blockade of the H1 receptor removed this effect of histamine. H1 receptor agonist (2-pyridylethlamine dihydrochloride) increased cell viability, thereby mimicking histamine action. Both Histamine (10 M) and 2-pyridylethlamine dihydrochloride increased TGFß1 concentration in cell culture medium. However, ketotifen blocked histamine-induced augmentation of TGFß1. H1 receptor expression on wound fibroblasts was confirmed. CONCLUSION: The regulatory influence of histamine on wound fibroblast function (viability/metabolic activity or secretion of TGFß1) is dependent on H1 receptor stimulation. Contrary to wound fibroblasts, these cells express a very low level of H1 receptors when isolated from intact dermis and histamine is unable to modify their metabolic activity.
[Mh] Termos MeSH primário: Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Fibroblastos/efeitos dos fármacos
Histamina/farmacologia
Fator de Crescimento Transformador beta1/metabolismo
Cicatrização/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Fibroblastos/metabolismo
Agonistas dos Receptores Histamínicos/farmacologia
Antagonistas dos Receptores Histamínicos H1/farmacologia
Masculino
Ratos
Ratos Wistar
Receptores Histamínicos H1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histamine Agonists); 0 (Histamine H1 Antagonists); 0 (Receptors, Histamine H1); 0 (Transforming Growth Factor beta1); 820484N8I3 (Histamine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170323
[Lr] Data última revisão:
170323
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170209
[St] Status:MEDLINE


  7 / 1225 MEDLINE  
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[PMID]:28103698
[Au] Autor:Teixeira MS; Alper CM; Martin BS; Cetin S; El-Wagaa JA; Doyle WJ
[Ad] Endereço:1 Department of Otolaryngology, School of Medicine of the University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
[Ti] Título:Histamine Applied Topically to the Nasal Mucosa Increases the Transmucosal Nitrous Oxide Exchange for the Middle Ear.
[So] Source:Ann Otol Rhinol Laryngol;126(4):284-289, 2017 Apr.
[Is] ISSN:1943-572X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Determine if the middle ear transmucosal nitrous oxide (N O) exchange rate is affected by nasal inflammation caused by topical application of histamine. METHODS: In a randomized, double-blind, crossover study, 20 adults were challenged intranasally with histamine (5 mg) and placebo on separate occasions. At each session, the subjects were fitted with a non-rebreathing mask and breathed room air for 20 minutes, 50% N O:50% O for 20 minutes, and 100% O for 10 minutes. Throughout, heart rate, blood pressure, and blood O saturation were monitored, and bilateral middle ear pressure was recorded by tympanometry every minute. The primary outcome measure was the slope of the middle ear pressure-time function for the 50% N O:50% O breathing period, which is a measure of the transmucosal N O exchange-constant. The effects of challenge substance, session, and period on the measured vital signs and of treatment, session, ear disease history, and test ear on the pressure-time slopes were evaluated using repeated measures ANOVAs. RESULTS: The post-challenge total symptom score and the slope of the middle ear pressure-time function were greater after histamine when compared to placebo challenge. Of the signs, only heart rate was affected, responding to challenge substance and study period. CONCLUSION: The transmucosal N O exchange rate for the middle ear is increased during inflammation caused by nasal histamine exposure.
[Mh] Termos MeSH primário: Orelha Média/efeitos dos fármacos
Agonistas dos Receptores Histamínicos/farmacologia
Histamina/farmacologia
Mucosa Nasal/efeitos dos fármacos
Óxido Nitroso/metabolismo
[Mh] Termos MeSH secundário: Testes de Impedância Acústica
Administração Intranasal
Administração Tópica
Adulto
Estudos Cross-Over
Método Duplo-Cego
Orelha Média/metabolismo
Feminino
Voluntários Saudáveis
Seres Humanos
Inflamação
Masculino
Meia-Idade
Mucosa Nasal/metabolismo
Fluxo Sanguíneo Regional
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Histamine Agonists); 820484N8I3 (Histamine); K50XQU1029 (Nitrous Oxide)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170417
[Lr] Data última revisão:
170417
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170121
[St] Status:MEDLINE
[do] DOI:10.1177/0003489416689470


  8 / 1225 MEDLINE  
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[PMID]:28040476
[Au] Autor:Hishinuma S; Kosaka K; Akatsu C; Uesawa Y; Fukui H; Shoji M
[Ad] Endereço:Department of Pharmacodynamics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. Electronic address: hishi@my-pharm.ac.jp.
[Ti] Título:Asp73-dependent and -independent regulation of the affinity of ligands for human histamine H receptors by Na .
[So] Source:Biochem Pharmacol;128:46-54, 2017 Mar 15.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The affinity of ligands for G-protein-coupled receptors (GPCRs) is allosterically regulated by Na via a highly conserved aspartate residue (Asp ) in the second transmembrane domain of GPCRs. In the present study, we examined the Na -mediated regulation of the affinity of ligands for G -protein-coupled human histamine H receptors in Chinese hamster ovary cells. The affinities of 3 agonists and 20 antihistamines were evaluated by their displacement curves against the binding of [ H]-mepyramine to membrane preparations in the presence or absence of 100mM NaCl. The affinities of most drugs including histamine, an agonist, and d-chlorpheniramine, a first-generation antihistamine, were reduced by NaCl, with the extent of NaCl-mediated changes varying widely between drugs. In contrast, the affinities of some second-generation antihistamines such as fexofenadine were increased by NaCl. These changes were retained in intact cells. The mutation of Asp (Asp73) to asparagine abrogated NaCl-induced reductions in affinities for histamine and d-chlorpheniramine, but not NaCl-induced increases in the affinity for fexofenadine. Quantitative structure-activity relationship (QSAR) analyses showed that these Na -mediated changes were explained and predicted by a combination of the molecular energies and implicit solvation energies of the compounds. These results suggest that Na diversely regulates the affinity of ligands for H receptors from the extracellular sites of receptors via Asp73-dependent and -independent mechanisms in a manner that depends on the physicochemical properties of ligands. These results may contribute to a deeper understanding of the fundamental mechanisms by which the affinity of ligands for their receptors is allosterically regulated by Na .
[Mh] Termos MeSH primário: Ácido Aspártico/genética
Receptores Histamínicos H1/fisiologia
Cloreto de Sódio/farmacologia
[Mh] Termos MeSH secundário: Animais
Células CHO
Cátions Monovalentes
Clorfeniramina/farmacologia
Cricetulus
Histamina/farmacologia
Agonistas dos Receptores Histamínicos/farmacologia
Antagonistas dos Receptores Histamínicos H1/farmacologia
Seres Humanos
Ligantes
Mutação
Relação Quantitativa Estrutura-Atividade
Ensaio Radioligante
Receptores Histamínicos H1/genética
Terfenadina/análogos & derivados
Terfenadina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cations, Monovalent); 0 (Histamine Agonists); 0 (Histamine H1 Antagonists); 0 (Ligands); 0 (Receptors, Histamine H1); 30KYC7MIAI (Aspartic Acid); 3U6IO1965U (Chlorpheniramine); 451W47IQ8X (Sodium Chloride); 7BA5G9Y06Q (Terfenadine); 820484N8I3 (Histamine); E6582LOH6V (fexofenadine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170502
[Lr] Data última revisão:
170502
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170102
[St] Status:MEDLINE


  9 / 1225 MEDLINE  
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[PMID]:27864425
[Au] Autor:Riddy DM; Cook AE; Diepenhorst NA; Bosnyak S; Brady R; Mannoury la Cour C; Mocaer E; Summers RJ; Charman WN; Sexton PM; Christopoulos A; Langmead CJ
[Ad] Endereço:Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (D.M.R., A.E.C., N.A.D., S.B., R.B., R.J.S., W.N.C., P.M.S., A.C., C.J.L.); and Institut de Recherches Internationales Servier, Suresnes, France (C.M.C., E.M.).
[Ti] Título:Isoform-Specific Biased Agonism of Histamine H3 Receptor Agonists.
[So] Source:Mol Pharmacol;91(2):87-99, 2017 Feb.
[Is] ISSN:1521-0111
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The human histamine H receptor (hH R) is subject to extensive gene splicing that gives rise to a large number of functional and nonfunctional isoforms. Despite the general acceptance that G protein-coupled receptors can adopt different ligand-induced conformations that give rise to biased signaling, this has not been studied for the H R; further, it is unknown whether splice variants of the same receptor engender the same or differential biased signaling. Herein, we profiled the pharmacology of histamine receptor agonists at the two most abundant hH R splice variants (hH R and hH R ) across seven signaling endpoints. Both isoforms engender biased signaling, notably for 4-[3-(benzyloxy)propyl]-1H-imidazole (proxyfan) [e.g., strong bias toward phosphorylation of glycogen synthase kinase 3ß (GSK3ß) via the full-length receptor] and its congener 3-(1H-imidazol-4-yl)propyl-(4-iodophenyl)-methyl ether (iodoproxyfan), which are strongly consistent with the former's designation as a "protean" agonist. The 80 amino acid IL3 deleted isoform hH R is more permissive in its signaling than hH R : 2-(1H-imidazol-5-yl)ethyl imidothiocarbamate (imetit), proxyfan, and iodoproxyfan were all markedly biased away from calcium signaling, and principal component analysis of the full data set revealed divergent profiles for all five agonists. However, most interesting was the identification of differential biased signaling between the two isoforms. Strikingly, hH R was completely unable to stimulate GSK3ß phosphorylation, an endpoint robustly activated by the full-length receptor. To the best of our knowledge, this is the first quantitative example of differential biased signaling via isoforms of the same G protein-coupled receptor that are simultaneously expressed in vivo and gives rise to the possibility of selective pharmacological targeting of individual receptor splice variants.
[Mh] Termos MeSH primário: Agonistas dos Receptores Histamínicos/farmacologia
Receptores Histamínicos H3/metabolismo
[Mh] Termos MeSH secundário: Animais
Bioensaio
Células CHO
Cricetinae
Cricetulus
AMP Cíclico/metabolismo
Agonistas dos Receptores Histamínicos/química
Seres Humanos
Análise de Componente Principal
Isoformas de Proteínas/metabolismo
Deleção de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histamine Agonists); 0 (Protein Isoforms); 0 (Receptors, Histamine H3); E0399OZS9N (Cyclic AMP)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161120
[St] Status:MEDLINE
[do] DOI:10.1124/mol.116.106153


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[PMID]:27787717
[Au] Autor:Schlicker E; Kathmann M
[Ad] Endereço:Institut für Pharmakologie und Toxikologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany. e.schlicker@uni-bonn.de.
[Ti] Título:Role of the Histamine H Receptor in the Central Nervous System.
[So] Source:Handb Exp Pharmacol;241:277-299, 2017.
[Is] ISSN:0171-2004
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The G protein-coupled histamine H receptor is distributed throughout the central nervous system including areas like cerebral cortex, hippocampus and striatum with the density being highest in the posterior hypothalamus, i.e. the area in which the histaminergic cell bodies are located. In contrast to the other histamine receptor subtypes (H , H and H ), the H receptor is located presynaptically and shows a constitutive activity. In detail, H receptors are involved in the inhibition of histamine release (presynaptic autoreceptor), impulse flow along the histaminergic neurones (somadendritic autoreceptor) and histamine synthesis. Moreover, they occur as inhibitory presynaptic heteroreceptors on serotoninergic, noradrenergic, dopaminergic, glutamatergic, GABAergic and perhaps cholinergic neurones. This review shows for four functions of the brain that the H receptor represents a brake against the wake-promoting, anticonvulsant and anorectic effect of histamine (via postsynaptic H receptors) and its procognitive activity (via postsynaptic H and H receptors). Indeed, H agonists and H inverse agonists elicit essentially the same effects, at least in rodents; these effects are opposite in direction to those elicited by brain-penetrating H receptor antagonists in humans. Although the benefit for H inverse agonists for the symptomatic treatment of dementias is inconclusive, several members of this group have shown a marked potential for the treatment of disorders associated with excessive daytime sleepiness. In March 2016, the European Commission granted a marketing authorisation for pitolisant (Wakix ) (as the first representative of the H inverse agonists) for the treatment of narcolepsy.
[Mh] Termos MeSH primário: Sistema Nervoso Central/metabolismo
Receptores Histamínicos H3/metabolismo
[Mh] Termos MeSH secundário: Animais
Anticonvulsivantes/farmacologia
Anticonvulsivantes/uso terapêutico
Sistema Nervoso Central/efeitos dos fármacos
Histamina/metabolismo
Agonistas dos Receptores Histamínicos/farmacologia
Agonistas dos Receptores Histamínicos/uso terapêutico
Antagonistas dos Receptores Histamínicos/farmacologia
Antagonistas dos Receptores Histamínicos/uso terapêutico
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Histamine Agonists); 0 (Histamine Antagonists); 0 (Receptors, Histamine H3); 820484N8I3 (Histamine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161028
[St] Status:MEDLINE
[do] DOI:10.1007/164_2016_12



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