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Heliyon Aug 2019Uridine 5'-triphosphate (UTP) exerts a positive inotropic effect (PIE) in isolated electrically driven isolated right atrial trabeculae carneae from patients undergoing... (Review)
Review
Uridine 5'-triphosphate (UTP) exerts a positive inotropic effect (PIE) in isolated electrically driven isolated right atrial trabeculae carneae from patients undergoing heart surgery. This review discusses some aspects of the current knowledge on the putative receptor(s) involved and the potential biochemical transduction steps leading to the PIE.
PubMed: 31406941
DOI: 10.1016/j.heliyon.2019.e02197 -
Peptides Nov 2009Melanin-concentrating hormone (MCH) is a cyclic peptide which was originally discovered in fish to lighten skin color by affecting melanosomes aggregation. This peptide... (Review)
Review
Melanin-concentrating hormone (MCH) is a cyclic peptide which was originally discovered in fish to lighten skin color by affecting melanosomes aggregation. This peptide is highly conserved and also found in rodents whose gene is overexpressed upon fasting. However, the site of MCH action remained obscure until its receptor was discovered in 1999 as a G protein-coupled receptor. After this receptor structure was identified, the functional domains important for MCH-MCHR interaction were revealed. Moreover, the cloning of the MCH receptor led us to identify the in vivo sites of MCH action which suggested potential physiological functions of the MCH system. Furthermore, the MCH receptor identification allow for designing surrogate molecules which can block MCH activity. Studies using these molecules revealed various physiological functions of the MCH system not only in feeding but also in other physiological responses such as stress and emotion. This review will discuss how the MCH receptor was discovered and its impact on many studies investigating the MCH receptor's structure, signaling pathways, and expression pattern.
Topics: Amino Acid Sequence; Animals; Brain; Gene Expression Regulation; Humans; Models, Biological; Molecular Sequence Data; Receptors, Pituitary Hormone; Salmon
PubMed: 19647772
DOI: 10.1016/j.peptides.2009.07.017 -
Frontiers in Immunology 2023Since the late 1970s, there has been an alarming increase in the incidence of asthma and its morbidity and mortality. Acute obstruction and inflammation of allergic... (Review)
Review
Since the late 1970s, there has been an alarming increase in the incidence of asthma and its morbidity and mortality. Acute obstruction and inflammation of allergic asthmatic airways are frequently caused by inhalation of exogenous substances such as allergens cross-linking IgE receptors expressed on the surface of the human lung mast cells (HLMC). The degree of constriction of human airways produced by identical amounts of inhaled allergens may vary from day to day and even hour to hour. Endogenous factors in the human mast cell (HMC)'s microenvironment during allergen exposure may markedly modulate the degranulation response. An increase in allergic responsiveness may significantly enhance bronchoconstriction and breathlessness. This review focuses on the role that the ubiquitous endogenous purine nucleotide, extracellular adenosine 5'-triphosphate (ATP), which is a component of the damage-associated molecular patterns, plays in mast cells' physiology. ATP activates P2 purinergic cell-surface receptors (P2R) to trigger signaling cascades resulting in heightened inflammatory responses. ATP is the most potent enhancer of IgE-mediated HLMC degranulation described to date. Current knowledge of ATP as it relates to targeted receptor(s) on HMC along with most recent studies exploring HMC post-receptor activation pathways are discussed. In addition, the reviewed studies may explain why brief, minimal exposures to allergens (e.g., dust, cat, mouse, and grass) can unpredictably lead to intense clinical reactions. Furthermore, potential therapeutic approaches targeting ATP-related enhancement of allergic reactions are presented.
Topics: Humans; Animals; Mice; Mast Cells; Signal Transduction; Adenosine Triphosphate; Asthma; Lung; Hypersensitivity; Allergens; Receptors, Purinergic P2
PubMed: 37868982
DOI: 10.3389/fimmu.2023.1216580 -
PLoS Pathogens Jan 2017African trypanosomes have complex life cycles comprising at least ten developmental forms, variously adapted to different niches in their tsetse fly vector and their... (Review)
Review
African trypanosomes have complex life cycles comprising at least ten developmental forms, variously adapted to different niches in their tsetse fly vector and their mammalian hosts. Unlike many other protozoan pathogens, they are always extracellular and have evolved intricate surface coats that allow them to obtain nutrients while also protecting them from the immune defenses of either insects or mammals. The acquisition of macromolecular nutrients requires receptors that function within the context of these surface coats. The best understood of these is the haptoglobin-hemoglobin receptor (HpHbR) of Trypanosoma brucei, which is used by the mammalian bloodstream form of the parasite, allowing heme acquisition. However, in some primates it also provides an uptake route for trypanolytic factor-1, a mediator of innate immunity against trypanosome infection. Recent studies have shown that during the evolution of African trypanosome species the receptor has diversified in function from a hemoglobin receptor predominantly expressed in the tsetse fly to a haptoglobin-hemoglobin receptor predominantly expressed in the mammalian bloodstream. Structural and functional studies of homologous receptors from different trypanosome species have allowed us to propose an evolutionary history for how one receptor has adapted to different roles in different trypanosome species. They also highlight the challenges that a receptor faces in operating on the complex trypanosome surface and show how these challenges can be met.
Topics: Animals; Biological Evolution; Humans; Immunity, Innate; Life Cycle Stages; Models, Molecular; Primates; Protozoan Proteins; Receptors, Cell Surface; Trypanosoma brucei brucei; Trypanosomiasis, African; Tsetse Flies
PubMed: 28125726
DOI: 10.1371/journal.ppat.1006055 -
Frontiers in Plant Science 2016The () gene encodes a leucine-rich repeat receptor-like protein, a class of cell surface receptors that lacks a cytoplasmic kinase domain. As such, CLV2 is capable of... (Review)
Review
The () gene encodes a leucine-rich repeat receptor-like protein, a class of cell surface receptors that lacks a cytoplasmic kinase domain. As such, CLV2 is capable of functioning in concert with additional receptor(s), possibly receptor-like kinase(s), to activate cellular responses upon ligand perception. Accumulating data indicate that CLV2 is implicated in distinct biological processes including plant growth and development as well as innate immunity to microbe and nematode infections. This article focuses on recent advances in our understanding of multiple signaling pathways mediated by multifunctional CLV2 that modulate various physiological processes. The challenges and future perspectives of elucidating the specificity of CLV2-mediated signaling pathways and identifying potential co-receptors and putative ligands for CLV2 are also discussed.
PubMed: 27822222
DOI: 10.3389/fpls.2016.01573 -
The Yale Journal of Biology and Medicine 1992Previous in vivo and in vitro studies from our laboratory have revealed a line of pharmacological evidence supporting histamine H3 receptor(s) involvement in the control... (Review)
Review
Previous in vivo and in vitro studies from our laboratory have revealed a line of pharmacological evidence supporting histamine H3 receptor(s) involvement in the control of gastric acid secretion. We have recently extended our studies to the human gastric tumoral cell HGT-1. This cell was found to contain an H3 receptor inhibiting basal and carbachol-stimulated inositol phosphate formation. Furthermore, we were able to solubilize and affinity-purify this receptor in the form of a single 70 kDa protein. These findings are the first biochemical description of the H3 receptor subtype and the first direct demonstration that this subtype can occur on a non-neural cell. Furthermore, they provide a molecular basis to explain its suggested inhibitory role in gastric physiology.
Topics: Animals; Gastric Acid; Humans; Receptors, Histamine H3; Stomach
PubMed: 1341067
DOI: No ID Found -
ACS Chemical Biology Feb 2021Intercellular signaling events mediated by neuropeptides and peptide hormones represent important targets for both basic science and drug discovery. For many bioactive... (Review)
Review
Intercellular signaling events mediated by neuropeptides and peptide hormones represent important targets for both basic science and drug discovery. For many bioactive peptides, the protein receptors that transmit information across the receiving cell membrane are not known, severely limiting these signaling pathways as potential therapeutic targets. Identifying the receptor(s) for a given peptide of interest is complicated by several factors. Most notably, cell-cell signaling peptides are generated through dynamic biosynthetic pathways, can act on many different families of receptor proteins, and can participate in complex ligand-receptor interactions that extend beyond a simple one-to-one archetype. Here, we discuss recent methodological advances to identify signaling partners for bioactive peptides. Recent efforts have centered on methods to identify candidate receptors via transcript expression, methods to match peptide-receptor pairs through high throughput screening, and methods to capture direct ligand-receptor interactions using chemical probes. Future applications of the receptor identification approaches discussed here, as well as technical advancements to address their limitations, promise to lead to a greater understanding of how cells communicate to deliver complex physiologies. Importantly, such advancements will likely provide novel targets for the treatment of human diseases within the central nervous and endocrine systems.
Topics: Animals; Humans; Ligands; Machine Learning; Molecular Probes; Neuropeptides; Peptide Hormones; Receptors, G-Protein-Coupled; Receptors, Neuropeptide
PubMed: 33539706
DOI: 10.1021/acschembio.0c00950 -
Journal of Innate Immunity 2009The interactions between Mycobacterium tuberculosis and host phagocytes such as macrophages and dendritic cells are central to both immunity and pathogenesis. Many... (Review)
Review
The interactions between Mycobacterium tuberculosis and host phagocytes such as macrophages and dendritic cells are central to both immunity and pathogenesis. Many receptors have been implicated in recognition and binding of M. tuberculosis such as the mannose receptor, dendritic-cell-specific intercellular adhesion molecule-3 grabbing nonintegrin, dectin-1 and complement receptor 3 as well as Toll-like receptors, scavenger receptors and CD14. While in vitro studies have demonstrated clear roles for particular receptor(s), in vivo work in receptor-deficient animals often revealed only a minor, or no role, in infection with M. tuberculosis. The initial encounter of phagocytic cells with myco- bacteria appears to be complex and depends on various parameters. It seems likely that infection with M. tuberculosis does not occur via a single receptor-mediated pathway. Rather, multiple receptors play different roles in M. tuberculosis infection, and the overall effect depends on the expression and availability of a particular receptor on a particular cell type and its triggered downstream responses. Moreover, the role of membrane cholesterol for M. tuberculosis interactions with phagocytes adds to the complexity of mycobacterial recognition and response. This review summarizes current knowledge on non-opsonic receptors involved in binding of mycobacteria and discusses the contribution of individual receptors to the recognition process.
Topics: Dendritic Cells; Humans; Immunity, Innate; Macrophages; Mycobacterium tuberculosis; Phagocytes; Receptors, Immunologic; Tuberculosis
PubMed: 20375581
DOI: 10.1159/000173703 -
ELife Nov 2012Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV)...
Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157-165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV.
Topics: Amino Acid Sequence; Animals; Cell Line, Tumor; Cells, Cultured; Disease Susceptibility; Hepatitis B; Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Hepatocytes; Humans; Ligands; Molecular Sequence Data; Organic Anion Transporters, Sodium-Dependent; Protein Binding; Protein Structure, Tertiary; Receptors, Virus; Reproducibility of Results; Symporters; Tupaiidae; Virion
PubMed: 25409679
DOI: 10.7554/eLife.00049 -
ENeuro 2015The growth hormone secretagogue receptor (GHSR1a), the target of the ghrelin peptide, is widely distributed throughout the brain, and, while studies have often reported... (Review)
Review
The growth hormone secretagogue receptor (GHSR1a), the target of the ghrelin peptide, is widely distributed throughout the brain, and, while studies have often reported very low or absent levels of central ghrelin, it is now known that GHSR1a, even in the absence of a natural ligand, has physiological roles. Not only do these roles originate from the receptor's constitutive activity, but recent data indicate that GHSR1a dimerizes with a wide array of other receptors. These include the dopamine 1 receptor (D1R), the dopamine 2 receptor (D2R), the melanocortin-3 receptor (MC3R), the serotonin 2C receptor (5-HT2C), and possibly the cannabinoid type 1 receptor (CB1). Within these dimers, signaling of the protomers involved are modified through facilitation, inhibition, and even modification of signaling pathways resulting in physiological consequences not seen in the absence of these dimers. While in some cases the ghrelin peptide is not required for these modifications to occur, in others, the presence is necessary for these changes to take effect. These heterodimers demonstrate the broad array of roles and complexity of the ghrelin system. By better understanding how these dimers work, it is hoped that improved treatments for a variety of disorders, including Parkinson's disease, schizophrenia, addiction, obesity, diabetes, and more, can be devised. In this review, we examine the current state of knowledge surrounding GHSR heterodimers, and how we can apply this knowledge to various pharmacological treatments.
PubMed: 26464979
DOI: 10.1523/ENEURO.0053-14.2015