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[PMID]: 29186716 [Au] Autor: Eichler W; Savkovic-Cvijic H; Bürger S; Beck M; Schmidt M; Wiedemann P; Reichenbach A; Unterlauft JD [Ad] Endereço: Department of Ophthalmology and Eye Hospital, Leipzig University, Leipzig, Germany. [Ti] Título: Müller Cell-Derived PEDF Mediates Neuroprotection via STAT3 Activation. [So] Source: Cell Physiol Biochem;44(4):1411-1424, 2017. [Is] ISSN: 1421-9778 [Cp] País de publicação: Switzerland [La] Idioma: eng [Ab] Resumo: Background/ Aims: This study was performed to reveal signaling pathways exploited by pigment epithelium-derived factor (PEDF) derived from retinal (glial) Müller cells to protect retinal ganglion cells (RGCs) from cell death. METHODS: The survival of RGCs was determined in the presence of conditioned culture media (MCM) from or in co-cultures with Müller cells. The significance of PEDF-induced STAT3 activation was evaluated in viability assays and using Western blotting analyses and siRNA-transfected cells. RESULTS: Secreted mediators of Müller cells increased survival of RGCs under normoxia or hypoxia to a similar degree as of PEDF- or IL-6-exposed cells. PEDF and MCM induced an increased STAT3 activation in RGCs and R28 cells, and neutralization of PEDF in MCM attenuated STAT3 activation. Inhibition of STAT3 reduced PEDF-promoted survival of RGCs. Similar to IL-6, PEDF induced STAT3 activation, acting in a dose-dependent manner via the PEDF receptor (PEDF-R) encoded by the PNPLA2 gene. Ablation of PEDF-R attenuated MCM-induced STAT3 activation and compromised the viability of PEDF-exposed R28 cells. CONCLUSIONS: Müller cells are an important source of PEDF, which promotes RGC survival through STAT3 activation and, at least in part, via PEDF-R. Enhancing the secretory function of Müller cells may be useful to promote RGC survival in retinal neurodegenerative diseases. [Mh] Termos MeSH primário: Células Ependimogliais/metabolismo Proteínas do Olho/metabolismo Fatores de Crescimento Neural/metabolismo Fator de Transcrição STAT3/metabolismo Serpinas/metabolismo [Mh] Termos MeSH secundário: Animais Hipóxia Celular Sobrevivência Celular/efeitos dos fármacos Técnicas de Cocultura Óxidos S-Cíclicos/farmacologia Células Ependimogliais/citologia Proteínas do Olho/antagonistas & inibidores Proteínas do Olho/genética Proteínas do Olho/farmacologia Interleucina-6/farmacologia Lipase/antagonistas & inibidores Lipase/genética Lipase/metabolismo Camundongos Fatores de Crescimento Neural/antagonistas & inibidores Fatores de Crescimento Neural/genética Fatores de Crescimento Neural/farmacologia Fosforilação/efeitos dos fármacos Interferência de RNA RNA Interferente Pequeno/metabolismo Ratos Receptores de Neuropeptídeos/metabolismo Células Ganglionares da Retina/metabolismo Fator de Transcrição STAT3/antagonistas & inibidores Serpinas/genética Serpinas/farmacologia Transdução de Sinais/efeitos dos fármacos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cyclic S-Oxides); 0 (Eye Proteins); 0 (Interleukin-6); 0 (Nerve Growth Factors); 0 (RNA, Small Interfering); 0 (Receptors, Neuropeptide); 0 (STAT3 Transcription Factor); 0 (Serpins); 0 (pigment epithelium-derived factor); 0 (pigment epithelium-derived factor receptor); 0 (stattic); EC 3.1.1.3 (Lipase) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180118 [Lr] Data última revisão: 180118 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171130 [St] Status: MEDLINE [do] DOI: 10.1159/000485537

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[PMID]: 28827148 [Au] Autor: Januliene D; Manavalan A; Ovesen PL; Pedersen KM; Thirup S; Nykjær A; Moeller A [Ad] Endereço: Department of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, 60438 Frankfurt am Main, Germany; DANDRITE, iNANO, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark. [Ti] Título: Hidden Twins: SorCS Neuroreceptors Form Stable Dimers. [So] Source: J Mol Biol;429(19):2907-2917, 2017 Sep 15. [Is] ISSN: 1089-8638 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: SorCS1, SorCS2 and SorCS3 belong to the Vps10p-domain family of multiligand receptors. Genetic and functional studies have linked SorCS receptors to psychiatric disorders, Alzheimer's disease and type 2 diabetes, demonstrating critical roles in neuronal functionality and metabolic control. Surprisingly, their structural composition has so far not been studied. Here we have characterized SorCS1, SorCS2 and SorCS3 using biochemical methods and electron microscopy. We found that their purified extracellular domains co-exist in stable dimeric and monomeric populations. This was supported by co-immunoprecipitation experiments, where membrane-bound dimers were successfully pulled down from cell lysate. While dimers were virtually unbreakable, dimerization of the monomeric population was promoted through enzymatic deglycosylation. We conclude that post-translational modifications, specifically the degree and pattern of glycosylation, regulate the oligomeric state of the protein. Hence, cells may dictate ligand specificity by controlling the ratio between monomers and dimers and, therefore, regulate the multiple functions of SorCS receptors. [Mh] Termos MeSH primário: Multimerização Proteica Receptores de Superfície Celular/química Receptores de Superfície Celular/metabolismo Receptores de Neuropeptídeos/química Receptores de Neuropeptídeos/metabolismo [Mh] Termos MeSH secundário: Imunoprecipitação Microscopia Eletrônica Processamento de Proteína Pós-Traducional [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Receptors, Cell Surface); 0 (Receptors, Neuropeptide); 0 (SORCS1 protein, human); 0 (SORCS2 protein, human); 0 (SorCS3 protein, human) [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: 170823 [St] Status: MEDLINE

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[PMID]: 28694291 [Au] Autor: Gupta K; Idahosa C; Roy S; Lee D; Subramanian H; Dhingra A; Boesze-Battaglia K; Korostoff J; Ali H [Ad] Endereço: Department of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA. [Ti] Título: Differential Regulation of Mas-Related G Protein-Coupled Receptor X2-Mediated Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas gingivalis Lipopolysaccharide. [So] Source: Infect Immun;85(10), 2017 Oct. [Is] ISSN: 1098-5522 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: is a keystone pathogen that contributes to periodontal pathogenesis by disrupting host-microbe homeostasis and promoting dysbiosis. The virulence of likely reflects an alteration in the lipid A composition of its lipopolysaccharide (LPS) from the penta-acylated ( LPS ) to the tetra-acylated ( LPS ) form. Mast cells play an important role in periodontitis, but the mechanisms of their activation and regulation remain unknown. The expression of epithelium- and neutrophil-derived host defense peptides (HDPs) (LL-37 and human ß-defensin-3), which activate mast cells via Mas-related G protein-coupled receptor X2 (MRGPRX2), is increased in periodontitis. We found that MRGPRX2-expressing mast cells are present in normal gingiva and that their numbers are elevated in patients with chronic periodontitis. Furthermore, HDPs stimulated degranulation in a human mast cell line (LAD2) and in RBL-2H3 cells stably expressing MRGPRX2 (RBL-MRGPRX2). LPS caused substantial inhibition of HDP-induced mast cell degranulation, but LPS had no effect. A fluorescently labeled HDP (FAM-LL-37) bound to RBL-MRGPRX2 cells, and LPS inhibited this binding, but LPS had no effect. These findings suggest that low-level inflammation induced by HDP/MRGPRX2-mediated mast cell degranulation contributes to gingival homeostasis but that sustained inflammation due to elevated levels of both HDPs and MRGPRX2-expressing mast cells promotes periodontal disease. Furthermore, differential regulation of HDP-induced mast cell degranulation by LPS and LPS may contribute to the modulation of disease progression. [Mh] Termos MeSH primário: Peptídeos Catiônicos Antimicrobianos/imunologia Infecções por Bacteroidaceae/imunologia Degranulação Celular Periodontite Crônica/imunologia Lipopolissacarídeos/imunologia Mastócitos/imunologia Proteínas do Tecido Nervoso/metabolismo Receptores Acoplados a Proteínas-G/metabolismo Receptores de Neuropeptídeos/metabolismo [Mh] Termos MeSH secundário: Peptídeos Catiônicos Antimicrobianos/química Peptídeos Catiônicos Antimicrobianos/metabolismo Linhagem Celular Periodontite Crônica/microbiologia Imunofluorescência Gengiva/imunologia Gengiva/microbiologia Gengiva/ultraestrutura Seres Humanos Lipopolissacarídeos/metabolismo Mastócitos/metabolismo Proteínas do Tecido Nervoso/genética Porphyromonas gingivalis/química Porphyromonas gingivalis/imunologia Porphyromonas gingivalis/metabolismo Receptores Acoplados a Proteínas-G/genética Receptores de Neuropeptídeos/genética beta-Defensinas/genética beta-Defensinas/imunologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antimicrobial Cationic Peptides); 0 (Lipopolysaccharides); 0 (MRGPRX2 protein, human); 0 (Nerve Tissue Proteins); 0 (Receptors, G-Protein-Coupled); 0 (Receptors, Neuropeptide); 0 (beta-Defensins); 0 (beta-defensin 3, human); 143108-26-3 (CAP18 lipopolysaccharide-binding protein) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171017 [Lr] Data última revisão: 171017 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170712 [St] Status: MEDLINE

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[PMID]: 28688196 [Au] Autor: Zhang T; Che D; Liu R; Han S; Wang N; Zhan Y; Pundir P; Cao J; Lv Y; Yang L; Wang J; Ding M; Dong X; He L [Ad] Endereço: School of Pharmacy, Xi'an Jiaotong University, Xi'an, China. [Ti] Título: Typical antimicrobials induce mast cell degranulation and anaphylactoid reactions via MRGPRX2 and its murine homologue MRGPRB2. [So] Source: Eur J Immunol;47(11):1949-1958, 2017 Nov. [Is] ISSN: 1521-4141 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: Mast cells are unique immune cells that function as sentinels in host defence reactions, including immediate hypersensitivity responses and allergic responses. The mast cell-specific receptor named MAS-related G protein-coupled receptor X2 (MRGPRX2) triggers mast-cell degranulation, a key process in anaphylactoid reactions. It is widely observed that antimicrobials can induce pseudo-allergic reactions (i.e. IgE-independent mechanism) with symptoms ranging from skin inflammation to life-threatening systemic anaphylaxis. However, their direct involvement and the mechanisms underlying anaphylactoid reactions caused by antimicrobials have not been demonstrated. Structurally different antimicrobials were screened by Ca imaging using MRGPRX2 overexpressing HEK293 cells. MRGPRX2 related anaphylactoid reactions induced by these components were investigated by body temperature drop and mast cell degranulation assays. We showed that MRGPRX2 is involved in allergic-like reactions to three types of antimicrobials in a dose-dependent manner. However, mast cells lacking the receptor show reduced degranulation. Furthermore, mice without MAS-related G protein-coupled receptor B2 (the orthologous gene of MRGPRX2) exhibited reduced substance-induced inflammation. Interestingly, ß-lactam and antiviral nucleoside analogues did not induce anaphylactic reactions, which were also observed in vitro. These results should alarm many clinicians that such drugs might induce anaphylactoid reactions and provide guidance on safe dosage of these drugs. [Mh] Termos MeSH primário: Anafilaxia/induzido quimicamente Anti-Infecciosos/toxicidade Degranulação Celular/efeitos dos fármacos Hipersensibilidade a Drogas/imunologia Mastócitos/efeitos dos fármacos Proteínas do Tecido Nervoso/imunologia Receptores Acoplados a Proteínas-G/imunologia Receptores de Neuropeptídeos/imunologia [Mh] Termos MeSH secundário: Animais Anti-Infecciosos/imunologia Células HEK293 Seres Humanos Masculino Camundongos Camundongos Endogâmicos C57BL Camundongos Knockout [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Infective Agents); 0 (MRGPRX2 protein, human); 0 (Mrgprb2 protein, mouse); 0 (Nerve Tissue Proteins); 0 (Receptors, G-Protein-Coupled); 0 (Receptors, Neuropeptide) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171113 [Lr] Data última revisão: 171113 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170709 [St] Status: MEDLINE [do] DOI: 10.1002/eji.201746951

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[PMID]: 28438614 [Au] Autor: Kovári B; Vranic S; Marchio C; Sapino A; Cserni G [Ad] Endereço: Department of Pathology, University of Szeged, 6720 Szeged, Hungary. Electronic address: kovari.bence.p@gmail.com. [Ti] Título: The expression of GHRH and its receptors in breast carcinomas with apocrine differentiation-further evidence of the presence of a GHRH pathway in these tumors. [So] Source: Hum Pathol;64:164-170, 2017 Jun. [Is] ISSN: 1532-8392 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Apocrine breast carcinomas were evaluated for the expression of components of the growth hormone-releasing hormone (GHRH) autocrine/paracrine pathway: GHRH and its receptors (GHRH-R), as mammary apocrine carcinomas and epithelium seemed to be uniformly positive for GHRH-R in a pilot study. The apocrine phenotype was determined on the basis of hematoxylin-eosin morphology and a congruent immunohistochemical profile (estrogen receptor negativity, androgen receptor and gross cystic disease fluid protein-15 positivity). Thirty-five formalin-fixed, paraffin-embedded apocrine breast cancers in tissue microarrays and 24 cases using whole-tissue sections were evaluated for GHRH-R and GHRH expression by immunohistochemistry using polyclonal antibodies raised against various domains of GHRH-R and one polyclonal antibody specific for GHRH. GHRH-R positivity was detected in the overwhelming majority (ranging from 90% to 100%) of apocrine breast carcinomas with all but one of the antibodies applied. The expression was usually diffuse with only isolated cases showing positivity in less than 50% of tumor cells. With the PA5-33583 antibody, GHRH-R positivity was seen only in 73% of the cases in at least 50% of the tumor cells. GHRH expression was also present in all but one case tested, with more than 50% of the cells expressing it in 30/34 cases. These results support a high rate of GHRH-R and GHRH expression in apocrine breast carcinomas. Whether these findings can be exploited for the targeted treatment of apocrine breast carcinomas with GHRH antagonists requires further study. [Mh] Termos MeSH primário: Glândulas Apócrinas/química Biomarcadores Tumorais/análise Neoplasias da Mama/química Carcinoma/química Hormônio Liberador de Hormônio do Crescimento/análise Receptores de Neuropeptídeos/análise Receptores de Hormônios Reguladores de Hormônio Hipofisário/análise [Mh] Termos MeSH secundário: Glândulas Apócrinas/patologia Biópsia Neoplasias da Mama/patologia Carcinoma/patologia Diferenciação Celular Feminino Seres Humanos Imuno-Histoquímica Estudos Retrospectivos Análise Serial de Tecidos Regulação para Cima [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Biomarkers, Tumor); 0 (Receptors, Neuropeptide); 0 (Receptors, Pituitary Hormone-Regulating Hormone); 0 (somatotropin releasing hormone receptor); 9034-39-3 (Growth Hormone-Releasing Hormone) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170911 [Lr] Data última revisão: 170911 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170426 [St] Status: MEDLINE

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[PMID]: 28288815 [Au] Autor: Elhabazi K; Humbert JP; Bertin I; Quillet R; Utard V; Schneider S; Schmitt M; Bourguignon JJ; Laboureyras E; Ben Boujema M; Simonnet G; Ancel C; Simonneaux V; Beltramo M; Bucher B; Sorg T; Meziane H; Schneider E; Petit-Demoulière B; Ilien B; Bihel F; Simonin F [Ad] Endereço: Biotechnologie et Signalisation Cellulaire, UMR 7242 CNRS, Université de Strasbourg, Laboratory of Excellence Médalis, Illkirch, France. Electronic address: elhabazi@unistra.fr. [Ti] Título: RF313, an orally bioavailable neuropeptide FF receptor antagonist, opposes effects of RF-amide-related peptide-3 and opioid-induced hyperalgesia in rodents. [So] Source: Neuropharmacology;118:188-198, 2017 May 15. [Is] ISSN: 1873-7064 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Although opiates represent the most effective analgesics, their use in chronic treatments is associated with numerous side effects including the development of pain hypersensitivity and analgesic tolerance. We recently identified a novel orally active neuropeptide FF (NPFF) receptor antagonist, RF313, which efficiently prevents the development of fentanyl-induced hyperalgesia in rats. In this study, we investigated the properties of this compound into more details. We show that RF313 exhibited a pronounced selectivity for NPFF receptors, antagonist activity at NPFF1 receptor (NPFF1R) subtype both in vitro and in vivo and no major side effects when administered in mice up to 30 mg/kg. When co-administered with opiates in rats and mice, it improved their analgesic efficacy and prevented the development of long lasting opioid-induced hyperalgesia. Moreover, and in marked contrast with the dipeptidic NPFF receptor antagonist RF9, RF313 displayed negligible affinity and no agonist activity (up to 100 µM) toward the kisspeptin receptor. Finally, in male hamster, RF313 had no effect when administered alone but fully blocked the increase in LH induced by RFRP-3, while RF9 per se induced a significant increase in LH levels which is consistent with its ability to activate kisspeptin receptors. Altogether, our data indicate that RF313 represents an interesting compound for the development of therapeutic tools aiming at improving analgesic action of opiates and reducing adverse side effects associated with their chronic administration. Moreover, its lack of agonist activity at the kisspeptin receptor indicates that RF313 might be considered a better pharmacological tool, when compared to RF9, to examine the regulatory roles of RF-amide-related peptides and NPFF1R in reproduction. [Mh] Termos MeSH primário: Analgésicos Opioides/uso terapêutico Hiperalgesia/tratamento farmacológico Antagonistas de Entorpecentes/uso terapêutico Oligopeptídeos/uso terapêutico Receptores de Neuropeptídeos/antagonistas & inibidores [Mh] Termos MeSH secundário: Administração Oral Animais Células CHO Cricetinae Cricetulus Modelos Animais de Doenças Fentanila/farmacologia Seres Humanos Masculino Mesocricetus Camundongos Camundongos Endogâmicos C57BL Oligopeptídeos/química Peptídeos/uso terapêutico Piperidinas/química Piperidinas/uso terapêutico Ligação Proteica/efeitos dos fármacos Ratos Ratos Sprague-Dawley Receptores de Neuropeptídeos/metabolismo Valina/análogos & derivados Valina/química Valina/uso terapêutico [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Analgesics, Opioid); 0 (Narcotic Antagonists); 0 (Oligopeptides); 0 (Peptides); 0 (Piperidines); 0 (RF313 compound); 0 (Receptors, Neuropeptide); 0 (neuropeptide FF receptor); 99566-27-5 (phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide); HG18B9YRS7 (Valine); UF599785JZ (Fentanyl) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170906 [Lr] Data última revisão: 170906 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170315 [St] Status: MEDLINE

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[PMID]: 28288109 [Au] Autor: Lansu K; Karpiak J; Liu J; Huang XP; McCorvy JD; Kroeze WK; Che T; Nagase H; Carroll FI; Jin J; Shoichet BK; Roth BL [Ad] Endereço: Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA. [Ti] Título: In silico design of novel probes for the atypical opioid receptor MRGPRX2. [So] Source: Nat Chem Biol;13(5):529-536, 2017 May. [Is] ISSN: 1552-4469 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The primate-exclusive MRGPRX2 G protein-coupled receptor (GPCR) has been suggested to modulate pain and itch. Despite putative peptide and small-molecule MRGPRX2 agonists, selective nanomolar-potency probes have not yet been reported. To identify a MRGPRX2 probe, we first screened 5,695 small molecules and found that many opioid compounds activated MRGPRX2, including (-)- and (+)-morphine, hydrocodone, sinomenine, dextromethorphan, and the prodynorphin-derived peptides dynorphin A, dynorphin B, and α- and ß-neoendorphin. We used these to select for mutagenesis-validated homology models and docked almost 4 million small molecules. From this docking, we predicted ZINC-3573-a potent MRGPRX2-selective agonist, showing little activity against 315 other GPCRs and 97 representative kinases-along with an essentially inactive enantiomer. ZINC-3573 activates endogenous MRGPRX2 in a human mast cell line, inducing degranulation and calcium release. MRGPRX2 is a unique atypical opioid-like receptor important for modulating mast cell degranulation, which can now be specifically modulated with ZINC-3573. [Mh] Termos MeSH primário: Simulação por Computador Desenho de Drogas Sondas Moleculares/síntese química Proteínas do Tecido Nervoso/agonistas Pirazóis/síntese química Pirazóis/farmacologia Pirimidinas/síntese química Pirimidinas/farmacologia Receptores Acoplados a Proteínas-G/agonistas Receptores de Neuropeptídeos/agonistas [Mh] Termos MeSH secundário: Cálcio/metabolismo Degranulação Celular/efeitos dos fármacos Linhagem Celular Relação Dose-Resposta a Droga Avaliação Pré-Clínica de Medicamentos Seres Humanos Ligantes Mastócitos/efeitos dos fármacos Mastócitos/secreção Simulação de Acoplamento Molecular Sondas Moleculares/química Sondas Moleculares/farmacologia Estrutura Molecular Proteínas do Tecido Nervoso/genética Proteínas do Tecido Nervoso/metabolismo Pirazóis/química Pirimidinas/química Receptores Acoplados a Proteínas-G/genética Receptores Acoplados a Proteínas-G/metabolismo Receptores de Neuropeptídeos/genética Receptores de Neuropeptídeos/metabolismo Relação Estrutura-Atividade [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Ligands); 0 (MRGPRX2 protein, human); 0 (Molecular Probes); 0 (Nerve Tissue Proteins); 0 (Pyrazoles); 0 (Pyrimidines); 0 (Receptors, G-Protein-Coupled); 0 (Receptors, Neuropeptide); 0 (ZINC-72453573); SY7Q814VUP (Calcium) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 171115 [Lr] Data última revisão: 171115 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170314 [St] Status: MEDLINE [do] DOI: 10.1038/nchembio.2334

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[PMID]: 28242309 [Au] Autor: Kitazawa T; Yoshida M; Teraoka H; Kaiya H [Ad] Endereço: School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan. Electronic address: tko-kita@rakuno.ac.jp. [Ti] Título: Does motilin peptide regulate gastrointestinal motility of zebrafish? An in vitro study using isolated intestinal strips. [So] Source: Gen Comp Endocrinol;249:15-23, 2017 Aug 01. [Is] ISSN: 1095-6840 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Motilin (MOT), a 22-amino-acid peptide hormone produced in the duodenal mucosa, stimulates gastrointestinal motility in mammals and birds, and it is a mediator of interdigestive motor complexes. Recently, expression of MOT-like peptide (MOTLP) and its receptor mRNAs was identified in zebrafish. The aim of the present study was to determine whether the zebrafish MOTLP (zfMOTLP, HIAFFSPKEMRELREKE) affects zebrafish gastrointestinal motility, with comparison to the effect of human MOT, in which five amino acids are identical to zfMOTLP at positions 5, 9, 15, 16, and 17. zfMOTLP caused small contractions of the rabbit duodenum and chicken ileum but, the sensitivity was about 3000-times lower than that of human MOT. zfMOTLP-induced contraction in the rabbit duodenum was decreased by pretreatment of the MOT receptor antagonist GM109, indicating that zfMOTLP could bind to the MOT receptor. zfMOTLP (3-100nM) increased the intracellular Ca concentration in zfMOT receptor-expressing HEK293 cells, but human MOT did not cause responses even at 100nM. In in vitro study using isolated zebrafish gastrointestinal strips, zfMOTLP caused only small contractions even at high doses (1-10µM). zfMOT receptor mRNA is detected in the gastrointestinal tract and brain to almost the same extent, and the expression level (40-70 copies/100ng total RNA) is much lower than that in the chicken gastrointestinal tract. These results suggest that the MOTLP/MOT receptor system is present in zebrafish, but its physiological role for regulation of gastrointestinal motility might be not significant due to the weak contractile activity and low expression level of the receptor. [Mh] Termos MeSH primário: Motilidade Gastrointestinal/fisiologia Intestinos/fisiologia Motilina/farmacologia [Mh] Termos MeSH secundário: Animais Galinhas Motilidade Gastrointestinal/efeitos dos fármacos Células HEK293 Seres Humanos Técnicas In Vitro Intestinos/efeitos dos fármacos Masculino Camundongos Contração Muscular/efeitos dos fármacos Peptídeos Cíclicos/farmacologia RNA Mensageiro/genética RNA Mensageiro/metabolismo Coelhos Receptores dos Hormônios Gastrointestinais/antagonistas & inibidores Receptores dos Hormônios Gastrointestinais/genética Receptores dos Hormônios Gastrointestinais/metabolismo Receptores de Neuropeptídeos/antagonistas & inibidores Receptores de Neuropeptídeos/genética Receptores de Neuropeptídeos/metabolismo Transfecção Peixe-Zebra/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (GM 109); 0 (Peptides, Cyclic); 0 (RNA, Messenger); 0 (Receptors, Gastrointestinal Hormone); 0 (Receptors, Neuropeptide); 0 (motilin receptor); 52906-92-0 (Motilin) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171106 [Lr] Data última revisão: 171106 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170301 [St] Status: MEDLINE

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[PMID]: 28239793 [Au] Autor: Masliuko PM; Anikina TA; Zverev AA; Krylova AV; Moiseev KY; Zefirov TL [Ad] Endereço: Department of Normal Physiology and Biophysics, Yaroslavl State Medical University, Yaroslavl, Russia. [Ti] Título: NPY Receptors Participate in the Regulation of Myocardial Contractility in Rats. [So] Source: Bull Exp Biol Med;162(4):418-420, 2017 Feb. [Is] ISSN: 1573-8221 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Selective agonist (Leu(31)Pro(34)NPY) and blocker (BIBP-3226) of NPY1 receptors were used to determine the type of NPY receptors involved in myocardial contraction. Experiments with isometric contraction of myocardial strips from mature rats showed that the agonist produced the most potent effect in a concentration of 10 M. In this concentration, Leu(31)Pro(34)NPY showed the greatest positive inotropic effect on the contraction of the atria and ventricles. In contrast, selective blocker BIBP-3226 reduced the force of myocardial contractions. Pretreatment of myocardial strips with this blocker abolished the positive inotropic effect of Leu(31)Pro(34)NPY, which attested to important role of NPY receptors in myocardial contraction. [Mh] Termos MeSH primário: Arginina/análogos & derivados Cardiotônicos/farmacologia Contração Isométrica/efeitos dos fármacos Contração Miocárdica/efeitos dos fármacos Neuropeptídeo Y/análogos & derivados Receptores Acoplados a Proteínas-G/metabolismo Receptores de Neuropeptídeos/metabolismo [Mh] Termos MeSH secundário: Animais Animais não Endogâmicos Arginina/farmacologia Relação Dose-Resposta a Droga Átrios do Coração/efeitos dos fármacos Átrios do Coração/metabolismo Ventrículos do Coração/efeitos dos fármacos Ventrículos do Coração/metabolismo Contração Isométrica/fisiologia Contração Miocárdica/fisiologia Miocárdio/metabolismo Neuropeptídeo Y/farmacologia Ratos Receptores Acoplados a Proteínas-G/agonistas Receptores Acoplados a Proteínas-G/antagonistas & inibidores Receptores de Neuropeptídeos/agonistas Receptores de Neuropeptídeos/antagonistas & inibidores Técnicas de Cultura de Tecidos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (BIBP 3226); 0 (Cardiotonic Agents); 0 (Neuropeptide Y); 0 (Npy1r protein, rat); 0 (Receptors, G-Protein-Coupled); 0 (Receptors, Neuropeptide); 125580-28-1 (neuropeptide Y, Leu(31)-Pro(34)-); 94ZLA3W45F (Arginine) [Em] Mês de entrada: 1703 [Cu] Atualização por classe: 170315 [Lr] Data última revisão: 170315 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170228 [St] Status: MEDLINE [do] DOI: 10.1007/s10517-017-3629-x

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MEDLINE

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[PMID]: 28199332 [Au] Autor: Chi L; Li X; Liu Q; Liu Y [Ad] Endereço: Center of Biotechnology R&D, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, P.R. China. [Ti] Título: Photoperiod regulate gonad development via kisspeptin/kissr in hypothalamus and saccus vasculosus of Atlantic salmon (Salmo salar). [So] Source: PLoS One;12(2):e0169569, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Atlantic salmon exhibit seasonal reproduction. However, the mechanisms governing this are still unclear. Generally speaking, kisspeptin has been recognized as a regulator of reproduction. Here, we report a relationship between kisspeptin, GnRH and photoperiod in Atlantic salmon. The results demonstrated that the expression of the Atlantic salmon kisspeptin-receptor (skissr) was not always consistent with the expression pattern of Atlantic salmon GnRH3 (sGnRH3) during all developmental processes. Kisspeptin may exert its influence primarily in the early and later stages of gonad development by promoting the secretion of sGnRH3. Meanwhile, the expression levels of kissr were higher in fish with gonads at stage II and stage V under the long-day photoperiod regime than under the short-day regime. In addition, both skissr and sGnRH3 were also expressed in the saccus vasculosus (SV), an organ only found in fish. The SV might be a seasonal sensor regulating reproduction in addition to the hypothalamus (Hyp). [Mh] Termos MeSH primário: Proteínas de Peixes/biossíntese Regulação da Expressão Gênica/fisiologia Gônadas/crescimento & desenvolvimento Hipotálamo/crescimento & desenvolvimento Fotoperíodo Receptores de Neuropeptídeos/biossíntese Salmo salar/crescimento & desenvolvimento [Mh] Termos MeSH secundário: Animais Feminino Hormônio Liberador de Gonadotropina/biossíntese Masculino Ácido Pirrolidonocarboxílico/análogos & derivados [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Fish Proteins); 0 (Receptors, Neuropeptide); 0 (gonadotropin-releasing hormone-III); 33515-09-2 (Gonadotropin-Releasing Hormone); SZB83O1W42 (Pyrrolidonecarboxylic Acid) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170809 [Lr] Data última revisão: 170809 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170216 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0169569

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