Christa Müller

Christa Müller
University of Bonn | Uni Bonn · Pharmaceutical Institute

About

182
Publications
18,147
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2,861
Citations
Citations since 2016
50 Research Items
1730 Citations
20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
20162017201820192020202120220100200300400

Publications

Publications (182)
Article
The pulp of human teeth contains a population of self-renewing stem cells that can regulate the functions of immune cells. When applied to patients, these cells can protect tissues from damage by excessive inflammation. We confirm that dental pulp cells effectively inhibit the proliferation and activation of cytotoxic T cells in vitro, and show tha...
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This review provides an overview of organic compounds detected in non-avian dinosaur fossils to date. This was enabled by the development of sensitive analytical techniques. Non-destructive methods and procedures restricted to the sample surface, e.g., light and electron microscopy, infrared (IR) and Raman spectroscopy, as well as more invasive app...
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Initial T cell activation is triggered by the formation of highly dynamic, spatiotemporally restricted Ca ²⁺ microdomains. Purinergic signaling is known to be involved in Ca ²⁺ influx in T cells at later stages compared to the initial microdomain formation. Using a high-resolution Ca ²⁺ live-cell imaging system, we show that the two purinergic cati...
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The G protein‐coupled adenosine A2A receptor (A2AAR) is an important new (potential) drug target in immuno‐oncology, and for neurodegenerative diseases. Preladenant and its derivatives belong to the most potent A2AAR antagonists displaying exceptional selectivity. While crystal structures of the human A2AAR have been solved, mostly using the A2A‐St...
Article
The G protein‐coupled adenosine A2A receptor (A2AAR) is an important new (potential) drug target in immuno‐oncology, and for neurodegenerative diseases. Preladenant and its derivatives belong to the most potent A2AAR antagonists displaying exceptional selectivity. While crystal structures of the human A2AAR have been solved, mostly using the A2A‐St...
Article
The development of neurodegenerative diseases is associated with cerebral inflammation, which activates resident immune cells of the central nervous system (CNS), namely microglial cells that show an up-regulation of the cannabinoid subtype 2 receptor (CB2R) expression. Therefore our work aimed to design and synthesize a radiotracer for the detecti...
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Heat sterilization of glucose solutions can lead to the formation of various glucose degradation products (GDPs) due to oxidation, hydrolysis, and dehydration. GDPs can have toxic effects after parenteral administration due to their high reactivity. In this study, the application of the F0 concept to modify specific time/temperature models during h...
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Immune cells at sites of inflammation are continuously activated by local antigens and cytokines, and regulatory mechanisms must be enacted to control inflammation. The stepwise hydrolysis of extracellular ATP by ectonucleotidases CD39 and CD73 generates adenosine, a potent immune suppressor. Here we report that human effector CD8 T cells contribut...
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The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targe...
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The main protease of SARS‐CoV‐2 (Mpro), the causative agent of COVID‐19, constitutes a significant drug target. A new fluorogenic substrate was kinetically compared to an internally quenched fluorescent peptide and shown to be ideally suitable for high throughput screening with recombinantly expressed Mpro. Two classes of protease inhibitors, azani...
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Die Hauptprotease (Mpro) von SARS‐CoV‐2 gilt als wichtige Arzneistoff‐Zielstruktur für die Therapie von COVID‐19. Das Design eines neuen fluorogenen Substrats, die rekombinante Expression von Mpro und die Entwicklung eines HTS‐Assays wurden mit einem Struktur‐basierten Ansatz kombiniert. Dieser führte zur Entdeckung maßgeschneiderter Azanitrile und...
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Porphyrins are macrocyclic tetrapyrrole derivatives that are widely distributed in nature. They are often complexed with a metal ion located in the center of the ring system and may be modified by various substituents including additional rings, or by ring opening, which leads to a plethora of different functions. Due to their extended conjugated a...
Article
Microglia cells are versatile players coordinating inflammatory and regenerative processes in the central nervous system in which sphingosine-1-phosphate (S1P)-mediated migration is essential. We investigated the involved signaling cascade by means of voltage clamp, measurement of ATP secretion, and wound healing assay in murine microglial BV-2 cel...
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The fossilization of soft tissues is generally the replacement of organic structures by pseudomorphs in which muscle tissue is mostly replaced by minerals (i.e., phosphate, carbonate or pyrite). Micro-CT observations of decomposing crayfish in tank and distilled water, show a precipitation of crystal clusters over time. In addition, a mineralized m...
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Amyotrophic Lateral Sclerosis (ALS) mostly affects motor neurons, but non-motor neural and cognitive alterations have been reported in ALS mouse models and patients. Here, we evaluated if time-dependent biphasic changes in synaptic transmission and plasticity occur in hippocampal synapses of ALS SOD1G93A mice. Recordings were performed in hippocamp...
Article
The complex nature of multifactorial diseases, such as Morbus Alzheimer, has produced a strong need to design multitarget-directed ligands to address the involved complementary pathways. We performed a purposive structural modification of a tetratarget small-molecule, that is contilisant, and generated a combinatorial library of 28 substituted chro...
Article
Nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) inhibitors have been suggested as a potential treatment for calcium pyrophosphate dihydrate (CPPD) deposition disease. Here, we targeted the development of improved NPP1 inhibitors based on acyclic mimics of Pα,α-phosphorodithioate-substituted adenine nucleotides, 7-10. The latter were obtained...
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Caffeine is the most consumed psychoactive stimulant and the main active ingredient of energy drinks. Epidemiology studies have shown a positive correlation between the consumption of energy drinks and that of ethanol. The popular belief is that caffeine antagonizes the intoxicating effects of alcohol. Both drugs act on the adenosine system but hav...
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Despite decades of research, only few drugs have been approved that interact with purine receptors. Recently, new hypes and hopes have been created in the field, mainly due to the gold rush fever in immuno-oncology. Adenosine is one of the strongest immunosuppressant agents of the innate immune system. Cancer cells and tissues can release large amo...
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Zubereitungen aus der Hanfpflanze Cannabis sativa werden seit Jahrtausenden als Genussdrogen und Arzneimittel eingesetzt. Die wichtigsten Inhaltsstoffe sind das psychoaktive (−)‑trans-∆⁹-Tetrahydrocannabinol (THC), das als Partialagonist an den Cannabinoid (CB)-Rezeptoren CB1 und CB2 fungiert, und das nicht psychoaktive, pleiotrop wirkende Cannabid...
Article
Ecto-nucleoside triphosphate diphosphohydrolase1 (NTPDase1, CD39) is a major ectonucleotidase that hydrolyzes proinflammatory ATP via ADP to AMP, which is subsequently converted by ecto-5’-nucleotidase (CD73) to immunosuppressive adenosine. Activation of CD39 has potential for treating inflammatory diseases, while inhibition was suggested as a nove...
Article
GPR18, still considered an orphan receptor, may respond to endocannabinoids, whose canonical receptors are CB1 and CB2. GPR18 and CB2 receptors share a role in peripheral immune response regulation and are co-expressed in microglia, which are immunocompetent cells in the central nervous system (CNS). We aimed at identifying heteroreceptor complexes...
Article
A library of 27 novel amide derivatives of annelated xanthines was designed and synthesized. The new compounds represent 1,3-dipropyl- and 1,3-dibutyl-pyrimido[2,1-f]purinedione-9-ethylphenoxy derivatives including a CH2CONH linker between (CH2)2-amino group and the phenoxy moiety. A synthetic strategy to obtain the final products was developed inv...
Article
We previously reported that uridine 5'-triphosphate (UTP), a pyrimidine nucleoside triphosphate produced a concentration- and time-dependent increase in the contraction force in isolated right atrial preparations from patients undergoing cardiac bypass surgery due to angina pectoris. The stimulation of the force of contraction was sustained rather...
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Adenosine represents a powerful modulating factor, which has been shown to orchestrate the scope, duration, and remission of the inflammatory response through the activation of four specific receptors, classified as A1, A2A, A2B, and A3, all being widely expressed in a variety of immune cells. Several selective A2A receptor agonists have displayed...
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P2X4 and P2X7 are members of the P2X receptor family, comprising seven isoforms (P2X1–P2X7) that form homo- and heterotrimeric non-specific cation channels gated by extracellular ATP. P2X4 and P2X7 are widely coexpressed, particularly in secretory epithelial cells and immune and inflammatory cells, and regulate inflammation and nociception. Althoug...
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Introduction: Mast cells play an important role in allergic responses. Methods: We herein demonstrated the mechanisms of inhibitory effect of adenine on IgE/antigen-induced degranulation and TNF-α release in mast cells. Results: We found that these effects were dependent on the amino group of adenine because purine only weakly inhibited degran...
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A fast and robust procedure for the quantification of GFP-tagged membrane proteins in cell homogenates was developed employing capillary gel electrophoresis coupled to laser-induced fluorescence detection (CGE-LIF). The new method was found to be highly sensitive and applicable to structurally diverse membrane proteins including synaptic vesicle pr...
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The GPR55 receptor is expressed abundantly in the brain, especially in the striatum, suggesting it might fulfill a role in motor function. Indeed, motor behavior is impaired in mice lacking GPR55, which also display dampened inflammatory responses. Abnormal-cannabidiol (Abn-CBD), a synthetic cannabidiol (CBD) isomer, is a GPR55 agonist that may ser...
Conference Paper
There are 334 extant species of marsupials, and 19 known herpesviruses that infect them. While much is known about herpesviruses that infect diverse groups of animals, the first marsupial herpesvirus genome was only published in 2016, that of a macropod simplex virus. In this study, we present the genomes of two gammaherpesviruses (one from koalas...
Article
Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1, EC 3.1.4.1) is a metalloenzyme that belongs to the NPP family, which comprises seven subtypes (NPP1-7). NPP1 hydrolyzes a wide range of phosphodiester bonds, e.g. in nucleoside triphosphates, (cyclic) dinucleotides, and nucleotide sugars yielding nucleoside 5′-monophosphates as products. It...
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Tardive dyskinesia (TD) is a serious motor side effect that may appear after long-term treatment with neuroleptics and mostly mediated by dopamine D2 receptors (D2Rs). Striatal D2R functioning may be finely regulated by either adenosine A2A receptor (A2AR) or angiotensin receptor type 1 (AT1R) through putative receptor heteromers. Here, we examined...
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Background: P2Y12 receptor antagonists are widely used in clinical practice to inhibit platelet aggregation. P2Y12 receptors are also known to regulate different forms of pain as well as local and systemic inflammation. However it is not known if platelet P2Y12 receptors contribute to these effects. Objectives: In this study, we explored the con...
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Together forever? Functional selection was applied to finally achieve separation of the analgesic properties of opiods from serious side effects such as potentially lethal respiratory depression. A Gi-biased μ-opioid-receptor agonist (PZM21) was identified that stabilizes previously unexplored receptor conformations. This compound relieves pain in...
Article
Up ewig ungedeelt? Funktionelle Selektivität ermöglicht endlich die Trennung von Schmerzhemmung und letaler Atemdepression! PZM21, ein Gi-Pfad-selektiver Agonist des μ-Opioid-Rezeptors, stabilisiert eine andere Rezeptorkonformation als Morphin und dämpft Schmerz bei Mäusen, ohne abhängig zu machen.
Article
Adenosine kinase (AdK) is a key player in controlling intra- and extracellular concentrations of the signaling molecule adenosine. Extensive evidence points to an important role of AdK in several diseases, and suggests that AdK inhibition might be a promising therapeutic strategy. The development of a new AdK assay and subsequent screening of part...
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The P2X7 receptor (P2X7R) has been reported as a key mediator in inflammatory processes and cancer invasion/metastasis. In this study, we report the discovery of novel P2X7R antagonists and their functional activities as potential anti-metastatic agents. Modifications of the hydantoin core-skeleton and the side chain substituents of P2X7R antagonis...
Article
A new series of 32 pyrimido- and 5 tetrahydropyrazino[2,1-f]purinediones was obtained and evaluated for their adenosine receptors (ARs) affinities. The 1,3-dibutyl derivative of 9-(4-(2-(dimethylamino)ethoxy)phenyl)-6,7,8,9-tetrahydropyrimido[1,2-f]purine-2,4(1H,3H)-dione was found to be the most potent A1 AR antagonist of the present series, showi...
Article
Erratum for A2A adenosine receptor deletion is protective in a mouse model of Tauopathy
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Despite the discovery of heterotrimeric αβγ G proteins ∼25 years ago, their selective perturbation by cell-permeable inhibitors remains a fundamental challenge. Here we report that the plant-derived depsipeptide FR900359 (FR) is ideally suited to this task. Using a multifaceted approach we systematically characterize FR as a selective inhibitor of...
Conference Paper
Full-text available
The purine nucleoside adenosine, which is involved in several physiological functions, regulates a variety of immune and inflammatory responses and acts as modulator of gut functions. Although it is present at low concentrations in the extracellular space, stressful conditions, such as inflammation can markedly increase its extracellular level up t...
Conference Paper
Das Purin-Nucleosid Adenosin reguliert eine Vielzahl von Immun- und Entzündungsantworten und wirkt als Modulator der Darmfunktion. Neueste Daten deuten auf eine wichtige Rolle des A2A-Rezeptors (A2AR) bei der entzündungshemmenden Wirkung von pflanzlichen Wirkstoffen wie Iberis-amara-Extrakt (STW 6) hin [1]. Auch für A2B-Rezeptoren (A2BR) wurde eine...
Article
A series of annelated derivatives of xanthine were synthesized and assayed as potential analgesic agents. All synthesized xanthine derivatives were tested in the writhing test and hot-plate test. The pharmacological assays demonstrated that all the compounds prepared, without exception, displayed a significant activity in the mouse writhing assay....
Article
Lithium still retains its critical position in the treatment of bipolar disorder by virtue of its ability to prevent suicidal tendencies. However, chronic use of lithium is often limited by the development nephrogenic diabetes insipidus (NDI), a debilitating condition. Lithium-induced NDI is due to resistance of the kidney to arginine vasopressin (...
Article
In 2002 the first receptor activated by the nucleobase adenine was discovered in rats. In the past years two adenine receptors (AdeRs) in mice and one in Chinese hamsters, all of which belong to the family of G protein-coupled receptors (GPCR) were cloned and pharmacologically characterized. Based on the nomenclature for other purinergic receptor f...
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Full text: http://www.nature.com/mp/journal/vaop/ncurrent/pdf/mp2014151a.pdf Consumption of caffeine, a non-selective adenosine A2A receptor (A2AR) antagonist, reduces the risk of developing Alzheimer's disease (AD) in humans and mitigates both amyloid and Tau burden in transgenic mouse models. However, the impact of selective A2AR blockade on the...
Article
Microglia, the resident immune cells of the CNS, get recruited to amyloid-β plaques in Alzheimer’s disease (AD) and it has been shown that microglia become functionally impaired in Alzheimer’s disease mouse models. Purinergic receptors have been described as mediators of microglial chemotaxis and phagocytosis. However, their role in AD remains elus...
Article
The development of nondopaminergic therapeutic strategies that may improve motor and nonmotor deficits, while possibly slowing down the neurodegenerative process and associated neuroinflammation,is a primary goal of Parkinson disease (PD) research. We investigated the neuroprotective and anti-inflammatory potential of combined and single treatment...
Article
GPR18 and GPR55 are orphan G protein-coupled receptors (GPCRs) that interact with certain cannabinoid (CB) receptor ligands. In the present study bicyclic imidazole-4-one derivatives were discovered as new scaffolds for the development of antagonists for GPR18 and GPR55. Interaction with CB1 and CB2 receptors was also studied to assess selectivity....
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Ticagrelor is a perorally available P2Y12 receptor antagonist used for the prevention of cardiovascular events. In the present study, we analyzed the mode of action of ticagrelor at the recombinant human P2Y12 receptor and mutant constructs stably expressed in CHO Flp-In cells. ADP and its analogue 2-methylthio-ADP (2-MeSADP) decreased forskolin-in...