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G protein-coupled receptors (GPCRs) respond to a chemically diverse plethora of signal transduction molecules. The notion that GPCRs also signal without an external chemical trigger, i.e., in a constitutive or spontaneous manner, resulted in a paradigm shift in the field of GPCR pharmacology. The discovery of constitutive GPCR activity and the fact that(More)
A three-dimensional homology model of the human histamine H 4 receptor was developed to investigate the binding mode of a series of structurally diverse H 4-agonists, i.e. histamine, clozapine, and the recently described selective, nonimidazole agonist VUF 8430. Mutagenesis studies and docking of these ligands in a rhodopsin-based homology model revealed(More)
Human cytomegalovirus (HCMV) encodes a G protein-coupled receptor (GPCR), named US28, which shows homology to chemokine receptors and binds several chemokines with high affinity. US28 induces migration of smooth muscle cells, a feature essential for the development of atherosclerosis, and may serve as a co-receptor for human immunodeficiency virus-type 1(More)
Using exome sequencing and linkage analysis in a three-generation family with a unique dominant myoclonus-dystonia-like syndrome with cardiac arrhythmias, we identified a mutation in the CACNA1B gene, coding for neuronal voltage-gated calcium channels CaV2.2. This mutation (c.4166G>A;p.Arg1389His) is a disruptive missense mutation in the outer region of the(More)
Hybrid drug 1 (NO-ASA) continues to attract intense research from chemists and biologists alike. It consists of ASA and a -ONO2 group connected through a spacer and is in preclinical development as an antitumor drug. We report that, contrary to current beliefs, neither ASA nor NO contributes to this antitumor effect. Rather, an unsubstituted QM was(More)
We tested several histamine H(1) receptor (H(1)R) and antagonists for their differences in agonists binding affinities between human and guinea pig H(1)Rs transiently expressed in African green monkey kidney (COS-7) cells. Especially, the bivalent agonist histaprodifen-histamine dimer (HP-HA) shows a higher affinity for guinea pig than for human H(1)Rs.(More)
Histamine H(1) antagonists or "antihistamines" are one of the most prescribed drug families in Western countries. They exert their effect by binding to the histamine H(1) receptor, a receptor belonging to the class of rhodopsin-like G protein-coupled receptors (GPCRs). In this review, the binding of ligands to the human histamine H(1) receptor with respect(More)
Tissue-resident memory T cells (TRM cells) in the airways mediate protection against respiratory infection. We characterized TRM cells expressing integrin αE (CD103) that reside within the epithelial barrier of human lungs. These cells had specialized profiles of chemokine receptors and adhesion molecules, consistent with their unique localization. Lung TRM(More)
Following the sequencing of the human genome, data-mining efforts have revealed the existence of a new histamine receptor that is expressed at high levels in mast cells and leukocytes. The histamine H(4) receptor has a distinct pharmacological profile and the first compounds that act selectively on the H(4) receptor have been developed. Initial experiments(More)
Rearrangement of transmembrane domains (TMs) 3 and 5 after agonist binding is necessary for stabilization of the active state of class A G protein-coupled receptors (GPCRs). Using site-directed mutagenesis and functional assays, we provide the first evidence that the TAS(I/V) sequence motif at positions 3.37 to 3.40, highly conserved in aminergic receptors,(More)