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[PMID]:28470555
[Au] Autor:Hong-Min F; Chun-Rong H; Rui Z; Li-Na S; Ya-Jun W; Li L
[Ad] Endereço:Comprehensive Pediatric Internal Department, Children's Hospital, Kunming Medical University, Kunming, 6500032, People's Republic of China.
[Ti] Título:CGRP 8-37 enhances lipopolysaccharide-induced acute lung injury and regulating aquaporin 1 and 5 expressions in rats.
[So] Source:J Physiol Biochem;73(3):381-386, 2016 Aug.
[Is] ISSN:1877-8755
[Cp] País de publicação:Spain
[La] Idioma:eng
[Ab] Resumo:Calcitonin gene-related peptide (CGRP) has been shown to play important roles in biological functions. However, there is very little evidence on the value of CGRP in lipopolysaccharide (LPS)-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Therefore, this study aimed to investigate the role of CGRP in LPS-induced ALI in rats. In the experiment, Sprague-Dawley (SD) rats were randomized into control, an antagonist of α-calcitonin gene-related peptide receptor (CGRP8-37), LPS groups, and CGRP8-37 + LPS groups. ALI model was prepared through retrograde injection of LPS (10 mg/kg). At 6 and 12 h, bronchoalveolar lavage was performed and used to assess total cell count and levels of tumor necrosis factor-α, interleukin-1ß, -6, and -10 by enzyme-linked immunosorbent assay (ELISA). Lung tissue was collected for assessing wet-to-dry (W/D) ratio, hematoxylin and eosin staining. Aquaporin (AQP)-1 and -5 expressions in lung tissues were detected by quantitative PCR and Western blot. The results showed that histological injury, total cell count, and W/D ratio significantly reduced in LPS group after 6 h. The levels of inflammatory cytokines in CGRP8-37 + LPS-treated rats were higher than that in LPS-treated rats (all, P < 0.001). Real-time RT-PCR analysis showed that levels of AQP-1 in rats from CGRP8-37 + LPS group was lower than that in LPS-treated rats (P = 0.005 and P < 0.001). Western blotting analysis showed that AQP-1 protein levels at 6 h significantly decreased in CGRP8-37 + LPS rats. Together, our data suggest that CGRP antagonists, CGRP8-37 could enhance ALI induced by LPS in the rat model, and regulate the expression levels of AQP-1 and AQP-5 by affecting inflammatory cytokines. Thereby, regulating endogenous CGRP may be a potential treatment for ALI/ARDS.
[Mh] Termos MeSH primário: Lesão Pulmonar Aguda/imunologia
Aquaporina 1/genética
Aquaporina 5/genética
Peptídeo Relacionado com Gene de Calcitonina/farmacologia
Fragmentos de Peptídeos/farmacologia
[Mh] Termos MeSH secundário: Lesão Pulmonar Aguda/metabolismo
Animais
Aquaporina 1/metabolismo
Aquaporina 5/metabolismo
Expressão Gênica/efeitos dos fármacos
Lipopolissacarídeos/farmacologia
Pulmão/imunologia
Pulmão/metabolismo
Pulmão/patologia
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aqp1 protein, rat); 0 (Aqp5 protein, rat); 0 (Aquaporin 5); 0 (Lipopolysaccharides); 0 (Peptide Fragments); 119911-68-1 (calcitonin gene-related peptide (8-37)); 146410-94-8 (Aquaporin 1); 83652-28-2 (Calcitonin Gene-Related Peptide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1007/s13105-017-0563-3


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[PMID]:27773630
[Au] Autor:Rahnama'i MS; Biallosterski BT; Van Kerrebroeck PE; van Koeveringe GA; Gillespie JI; de Wachter SG
[Ad] Endereço:Department of Urology, Maastricht University Medical Centre, POB 5800, 6202 AZ, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), The Department of Psychiatry and Neuropsychology, Maastricht University, POB 616, 6200 MD, Maastricht, The Netherlands. Electronic address: s
[Ti] Título:Distribution and sub-types of afferent fibre in the mouse urinary bladder.
[So] Source:J Chem Neuroanat;79:1-11, 2017 Jan.
[Is] ISSN:1873-6300
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIM: Increased afferent fibre activity contributes to pathological conditions such as the overactive bladder syndrome. Nerve fibres running near the urothelium are considered to be afferent as no efferent system has yet been described. The aim of this study was to identify sub-types of afferent nerve fibres in the mouse bladder wall based on morphological criteria and analyse regional differences. MATERIALS AND METHODS: 27 bladders of six month old C57BL/6 mice were removed and tissues were processed for immunohistochemistry. Cryostat sections were cut and stained for Protein Gene Product 9.5 (PGP), calcitonin gene related polypeptide (CGRP), neurofilament (NF), vesicular acetylcholine transporter (VAChT) and neuronal nitric oxide synthase (nNOS). RESULTS: In the sub-urothelium, different types of afferent nerve fibre were found, i.e. immunoreactive (IR) to; CGRP, NF, VAChT, and/or nNOS. At the bladder base, the sub-urothelium was more densely innervated by CGRP-IR and VAChT-IR nerve fibres, then at the lateral wall. NF- and nNOS nerves were sparsely distributed in the sub-urothelium throughout the bladder. At the lateral wall the inner muscle is densely innervated by CGRP-IR nerve fibres. NF, VAChT and nNOS nerves were evenly distributed in the different muscle layers throughout the bladder. Nerve fibre terminals expressing CGRP and NF were found within the extra-mural ganglia at the bladder base. CONCLUSIONS: Different types of afferent nerve fibres were identified in the sub-urothelium of the mouse bladder. At the bladder base the sub-urothelium is more densely innervated than the lateral wall by CGRP-IR and VAChT-IR afferent nerve fibres. CGRP and NF afferent nerve fibres in the muscle layer probably relay afferent input to external ganglia located near the bladder base. The identification of different afferent nerves in the sub-urothelium suggests a functional heterogeneity of the afferent nerve fibres in the urinary bladder.
[Mh] Termos MeSH primário: Fibras Nervosas/metabolismo
Neurônios Aferentes/metabolismo
Bexiga Urinária/inervação
Bexiga Urinária/metabolismo
[Mh] Termos MeSH secundário: Animais
Peptídeo Relacionado com Gene de Calcitonina/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Fibras Nervosas/química
Neurônios Aferentes/química
Óxido Nítrico Sintase Tipo I/metabolismo
Bexiga Urinária/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
83652-28-2 (Calcitonin Gene-Related Peptide); EC 1.14.13.39 (Nitric Oxide Synthase Type I); EC 1.14.13.39 (Nos1 protein, mouse)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161030
[St] Status:MEDLINE


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[PMID]:28452955
[Au] Autor:Grässel S; Muschter D
[Ad] Endereço:Department of Orthopedic Surgery, Exp. Orthopedics, ZMB/Biopark 1, University of Regensburg, 93053 Regensburg, Germany. susanne.graessel@ukr.de.
[Ti] Título:Peripheral Nerve Fibers and Their Neurotransmitters in Osteoarthritis Pathology.
[So] Source:Int J Mol Sci;18(5), 2017 Apr 28.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:The importance of the nociceptive nervous system for maintaining tissue homeostasis has been known for some time, and it has also been suggested that organogenesis and tissue repair are under neuronal control. Changes in peripheral joint innervation are supposed to be partly responsible for degenerative alterations in joint tissues which contribute to development of osteoarthritis. Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters, allowing response to peripheral neuronal stimuli. Among them are mesenchymal stem cells, synovial fibroblasts, bone cells and chondrocytes of different origin, which express distinct subtypes of adrenoceptors (AR), receptors for vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP). Some of these cell types synthesize and secrete neuropeptides such as SP, and they are positive for tyrosine-hydroxylase (TH), the rate limiting enzyme for biosynthesis of catecholamines. Sensory and sympathetic neurotransmitters are involved in the pathology of inflammatory diseases such as rheumatoid arthritis (RA) which manifests mainly in the joints. In addition, they seem to play a role in pathogenesis of priori degenerative joint disorders such as osteoarthritis (OA). Altogether it is evident that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for joint tissue and bone homeostasis. They modulate articular cartilage, subchondral bone and synovial tissue properties in physiological and pathophysiological conditions, in addition to their classical neurological features.
[Mh] Termos MeSH primário: Neurotransmissores/metabolismo
Osteoartrite/patologia
Nervos Periféricos/metabolismo
[Mh] Termos MeSH secundário: Peptídeo Relacionado com Gene de Calcitonina/metabolismo
Condrócitos/citologia
Condrócitos/metabolismo
Seres Humanos
Neuropeptídeos/metabolismo
Osteoartrite/metabolismo
Receptores Adrenérgicos/metabolismo
Substância P/metabolismo
Peptídeo Intestinal Vasoativo/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Neuropeptides); 0 (Neurotransmitter Agents); 0 (Receptors, Adrenergic); 33507-63-0 (Substance P); 37221-79-7 (Vasoactive Intestinal Peptide); 83652-28-2 (Calcitonin Gene-Related Peptide)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180122
[Lr] Data última revisão:
180122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:28455390
[Au] Autor:Christian WV; Hinkle PM
[Ad] Endereço:Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, U.S.A.
[Ti] Título:Global functions of extracellular, transmembrane and cytoplasmic domains of organic solute transporter ß-subunit.
[So] Source:Biochem J;474(12):1981-1992, 2017 05 25.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Transport of bile acids across the basolateral membrane of the intestinal enterocyte is carried out by the organic solute transporter (Ost) composed of a seven-transmembrane domain (TMD) subunit (Ostα) and an ancillary single TMD subunit (Ostß). Although previous investigations have demonstrated the importance of the TMD of Ostß for its activity, further studies were conducted to assess the contributions of other regions of the Ostß subunit. Transport activity was retained when Ostß was truncated to contain only the TMD with 15 additional residues on each side and co-expressed with Ostα, whereas shorter fragments were inactive. To probe the broader functions of Ostß segments, chimeric proteins were constructed in which N-terminal, TMD or C-terminal regions of Ostß were fused to corresponding regions of receptor activity-modifying protein (RAMP1), a single TMD protein required by several seven-TMD G-protein-coupled receptors including the calcitonin receptor-like receptor (CLR). Ostß/RAMP1 chimeras were expressed with Ostα and CLR. As expected, replacing the Ostß TMD abolished transport activity; however, replacing either the entire N-terminal or entire C-terminal domain of Ostß with RAMP1 sequences did not prevent plasma membrane localization or the ability to support [ H]taurocholate uptake. Co-immunoprecipitation experiments revealed that the C-terminus of Ostß is a previously unrecognized site of interaction with Ostα. All chimeras containing N-terminal RAMP1 segments allowed co-expressed CLR to respond to agonists with strong increases in cyclic AMP. These results provide new insights into the structure and function of the heteromeric Ost transporter complex.
[Mh] Termos MeSH primário: Ácidos e Sais Biliares/metabolismo
Proteínas de Membrana Transportadoras/metabolismo
[Mh] Termos MeSH secundário: Absorção Fisiológica/efeitos dos fármacos
Animais
Transporte Biológico/efeitos dos fármacos
Peptídeo Relacionado com Gene de Calcitonina/genética
Peptídeo Relacionado com Gene de Calcitonina/metabolismo
Proteína Semelhante a Receptor de Calcitonina/agonistas
Proteína Semelhante a Receptor de Calcitonina/genética
Proteína Semelhante a Receptor de Calcitonina/metabolismo
AMP Cíclico/metabolismo
Células HEK293
Seres Humanos
Imunoprecipitação
Proteínas de Membrana Transportadoras/química
Proteínas de Membrana Transportadoras/genética
Camundongos
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Domínios e Motivos de Interação entre Proteínas
Transporte Proteico
Proteína 1 Modificadora da Atividade de Receptores/química
Proteína 1 Modificadora da Atividade de Receptores/genética
Proteína 1 Modificadora da Atividade de Receptores/metabolismo
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Sistemas do Segundo Mensageiro/efeitos dos fármacos
Homologia Estrutural de Proteína
Ácido Taurocólico/metabolismo
Trítio
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Bile Acids and Salts); 0 (CALCA protein, human); 0 (CALCRL protein, human); 0 (Calcitonin Receptor-Like Protein); 0 (Membrane Transport Proteins); 0 (Peptide Fragments); 0 (Ramp1 protein, mouse); 0 (Receptor Activity-Modifying Protein 1); 0 (Recombinant Fusion Proteins); 0 (organic solute transporter alpha, mouse); 0 (organic solute transporter beta, mouse); 10028-17-8 (Tritium); 5E090O0G3Z (Taurocholic Acid); 83652-28-2 (Calcitonin Gene-Related Peptide); E0399OZS9N (Cyclic AMP)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171217
[Lr] Data última revisão:
171217
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20161093


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[PMID]:28387421
[Au] Autor:Gerbaud P; Guibourdenche J; Jarray R; Conti M; Palmic P; Leclerc-Mercier S; Bruneau J; Hermine O; Lepelletier Y; Raynaud F
[Ad] Endereço:INSERM, Université Paris Descartes, Paris, France.
[Ti] Título:APN/CD13 is over-expressed by Psoriatic fibroblasts and is modulated by CGRP and IL-4 but not by retinoic acid treatment.
[So] Source:J Cell Physiol;233(2):958-967, 2018 Feb.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Psoriasis vulgaris is a common skin inflammatory disease characterized by recurrent flare episodes associated with scaly well-demarcated skin plaques. Skin biopsies from psoriatic patients with high PASI score (22.67 ± 8.67) and from HD were used to study APN/CD13. APN/CD13 is over-expressed in LP and nLP compare to HD skins and fibroblasts. This over-expression is positively correlated with specific enzymatic activity enhancement. However, discrepancies between APN/CD13 expression in LP and nLP prompt us to focus our study on APN/CD13 modulation. Calcitonin Gene Related Peptide (CGRP), a neuropeptide, positively modulated expression and activity of APN/CD13. CGRP consistently induced IL4 secretion, which is also involved in the increase of APN/CD13 expression and activity, which is significantly reversed using IL-4 blocking antibody. Surprisingly, retinoic acid altered the APN/CD13 enzymatic activity only in nLP fibroblasts without modification of APN/CD13 expression. APN/CD13 is over-expressed on psoriatic fibroblasts and exerted high level of activity compare to HD fibroblasts. Taken together, several factors such as CGRP and IL-4 acted on positive regulation of APN/CD13 expression and activity. This study highlighted the interest of APN/CD13 as a new potential target, which should be investigated in psoriasis.
[Mh] Termos MeSH primário: Antígenos CD13/metabolismo
Peptídeo Relacionado com Gene de Calcitonina/farmacologia
Fibroblastos/efeitos dos fármacos
Interleucina-4/farmacologia
Psoríase/enzimologia
Pele/efeitos dos fármacos
Tretinoína/farmacologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Antígenos CD13/genética
Estudos de Casos e Controles
Células Cultivadas
Feminino
Fibroblastos/enzimologia
Fibroblastos/patologia
Seres Humanos
Masculino
Meia-Idade
Psoríase/genética
Psoríase/patologia
Pele/enzimologia
Pele/patologia
Fatores de Tempo
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IL4 protein, human); 207137-56-2 (Interleukin-4); 5688UTC01R (Tretinoin); 83652-28-2 (Calcitonin Gene-Related Peptide); EC 3.4.11.2 (CD13 Antigens)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170408
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.25941


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[PMID]:28972120
[Au] Autor:Melo-Carrillo A; Strassman AM; Nir RR; Schain AJ; Noseda R; Stratton J; Burstein R
[Ad] Endereço:Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215.
[Ti] Título:Fremanezumab-A Humanized Monoclonal Anti-CGRP Antibody-Inhibits Thinly Myelinated (Aδ) But Not Unmyelinated (C) Meningeal Nociceptors.
[So] Source:J Neurosci;37(44):10587-10596, 2017 Nov 01.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Calcitonin gene-related peptide (CGRP), the most abundant neuropeptide in primary afferent sensory neurons, is strongly implicated in the pathophysiology of migraine headache, but its role in migraine is still equivocal. As a new approach to migraine treatment, humanized anti-CGRP monoclonal antibodies (CGRP-mAbs) were developed to reduce the availability of CGRP, and were found effective in reducing the frequency of chronic and episodic migraine. We recently tested the effect of fremanezumab (TEV-48125), a CGRP-mAb, on the activity of second-order trigeminovascular dorsal horn neurons that receive peripheral input from the cranial dura, and found a selective inhibition of high-threshold but not wide-dynamic range class of neurons. To investigate the basis for this selective inhibitory effect, and further explore the mechanism of action of CGRP-mAbs, we tested the effect of fremanezumab on the cortical spreading depression-evoked activation of mechanosensitive primary afferent meningeal nociceptors that innervate the cranial dura, using single-unit recording in the trigeminal ganglion of anesthetized male rats. Fremanezumab pretreatment selectively inhibited the responsiveness of Aδ neurons, but not C-fiber neurons, as reflected in a decrease in the percentage of neurons that showed activation by cortical spreading depression. These findings identify Aδ meningeal nociceptors as a likely site of action of fremanezumab in the prevention of headache. The selectivity in its peripheral inhibitory action may partly account for fremanezumab's selective inhibition of high-threshold, as a result of a predominant A-δ input to high-threshold neurons, but not wide dynamic-range dorsal horn neurons, and why it may not be effective in all migraine patients. Recently, we reported that humanized CGRP monoclonal antibodies (CGRP-mAbs) prevent activation and sensitization of high-threshold (HT) but not wide-dynamic range trigeminovascular neurons by cortical spreading depression (CSD). In the current paper, we report that CGRP-mAbs prevent the activation of Aδ but not C-type meningeal nociceptors by CSD. This is the first identification of an anti-migraine drug that appears to be selective for Aδ-fibers (peripherally) and HT neurons (centrally). As the main CGRP-mAb site of action appears to be situated outside the brain, we conclude that the initiation of the headache phase of migraine depends on activation of meningeal nociceptors, and that for selected patients, activation of the Aδ-HT pain pathway may be sufficient for the generation of headache perception.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/farmacologia
Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores
Bainha de Mielina/efeitos dos fármacos
Fibras Nervosas Mielinizadas/efeitos dos fármacos
Fibras Nervosas Amielínicas/efeitos dos fármacos
Nociceptores/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Peptídeo Relacionado com Gene de Calcitonina/fisiologia
Seres Humanos
Masculino
Bainha de Mielina/fisiologia
Fibras Nervosas Mielinizadas/fisiologia
Fibras Nervosas Amielínicas/fisiologia
Nociceptores/fisiologia
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (TEV-48125); 83652-28-2 (Calcitonin Gene-Related Peptide)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171117
[Lr] Data última revisão:
171117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.2211-17.2017


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[PMID]:28898282
[Au] Autor:Ding S; Zhu L; Tian Y; Zhu T; Huang X; Zhang X
[Ad] Endereço:Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China.
[Ti] Título:P2X3 receptor involvement in endometriosis pain via ERK signaling pathway.
[So] Source:PLoS One;12(9):e0184647, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The purinergic receptor P2X ligand-gated ion channel 3 (P2X3) is crucially involved in peripheral nociceptive processes of somatic and visceral pain. Endometriosis pain is considered as a kind of inflammatory and neuropathic pain. However, whether P2X3 is involved in endometriosis pain has not been reported up to date. Here, we aimed to determine whether P2X3 expression in endometriotic lesions is involved in endometriosis pain, which is regulated by inflammatory mediators through extracellular regulated protein kinases (ERK) signalling pathway. We found that P2X3 expressions in endometriosis endometrium and endometriotic lesions were both significantly higher as compared with control endometrium (P<0.05), and both positively correlated with pain (P<0.05). The expression levels of phosphorylated -ERK (p-ERK), phosphorylated-cAMP-response element binding protein (p-CREB), and P2X3 in endometriotic stromal cells (ESCs) were all significantly increased in comparison to the initial levels after treated with interleukin (IL)-1ß (P<0.05) or adenosine triphosphate (ATP) (P<0.05), respectively, and did not increase after the ESCs were pre-treated with ERK1/2 inhibitor. Additionally, P2X3 and calcitonin gene related peptide (CGRP) were co-expressed in endometriotic lesions. These obtained results suggest that P2X3 might be involved in endometriosis pain signal transduction via ERK signal pathway.
[Mh] Termos MeSH primário: Endometriose/metabolismo
Proteína Quinase 1 Ativada por Mitógeno/metabolismo
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Receptores Purinérgicos P2X3/metabolismo
Dor Visceral/metabolismo
[Mh] Termos MeSH secundário: Adulto
Peptídeo Relacionado com Gene de Calcitonina/metabolismo
Estudos de Casos e Controles
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo
Endometriose/patologia
Feminino
Seres Humanos
Sistema de Sinalização das MAP Quinases
Receptores Purinérgicos P2X3/genética
Células Estromais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclic AMP Response Element-Binding Protein); 0 (Receptors, Purinergic P2X3); 83652-28-2 (Calcitonin Gene-Related Peptide); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184647


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[PMID]:28892747
[Au] Autor:Duan JX; Zhou Y; Zhou AY; Guan XX; Liu T; Yang HH; Xie H; Chen P
[Ad] Endereço:Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Research Unit of Respiratory Disease, Central South University, Changsha 410011, Hunan, China; Diagnosis and Treatment Center of Respiratory Disease, Central South University, Ch
[Ti] Título:Calcitonin gene-related peptide exerts anti-inflammatory property through regulating murine macrophages polarization in vitro.
[So] Source:Mol Immunol;91:105-113, 2017 11.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Acute lung injury (ALI) is a condition resulting from direct or indirect lung injury associated with high mortality and morbidity. The phenotype of macrophages in lung contributes to the pathological progress of ALI. Calcitonin gene-related peptide (CGRP) is one of the most abundant neuropeptides in lung, and attenuates lipopolysaccharide (LPS)-induced ALI in rats. However, the exact effect of CGRP on the activation of macrophages remains unknown. Here we investigate the effect of CGRP on the macrophages activation and inflammation in murine macrophages in vitro. We found that LPS increased the expression of CGRP in a LPS-induced ALI murine model and LPS-stimulated murine macrophages. Although CGRP didn't alter the expression of tumor necrosis factor-α (a marker of pro-inflammatory phenotype of macrophages, M1 macrophages) or Arginase 1 (Arg1, a marker of M2 macrophages) in non-differentiated macrophages, CGRP significantly reduced the NLRP3 and pro-IL-1ß mRNA expression induced by LPS, as well as NLRP3 protein and IL-1ß secretion induced by LPS+ATP in macrophages in vitro. On the other hand, CGRP dramatically enhanced the Arg1 expression and activity induced by IL-4 in the time- and dose-dependent manners. CGRP also promoted the expression of markers of M2 macrophages (IL-10, Fizz1 and Mrc1) induced by IL-4 in murine macrophages. These effects of CGRP were also observed in primary murine peritoneal macrophages. In addition, we found that CGRP regulated macrophages polarization partially through calmodulin, PKC and PKA pathways. Specifically, CGRP could inhibit the degradation of I-κB induced by LPS, and enhance the phosphorylation of STAT6 induced by IL-4 in macrophages. In conclusion, our results indicate that CGRP regulates macrophage polarization and inhibits inflammation in murine macrophages.
[Mh] Termos MeSH primário: Lesão Pulmonar Aguda/imunologia
Peptídeo Relacionado com Gene de Calcitonina/imunologia
Macrófagos/imunologia
[Mh] Termos MeSH secundário: Lesão Pulmonar Aguda/induzido quimicamente
Lesão Pulmonar Aguda/patologia
Animais
Antígenos de Diferenciação/imunologia
Citocinas/imunologia
Modelos Animais de Doenças
Proteínas I-kappa B/imunologia
Lipopolissacarídeos/toxicidade
Macrófagos/patologia
Masculino
Camundongos
Ratos
Fator de Transcrição STAT6/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, Differentiation); 0 (Cytokines); 0 (I-kappa B Proteins); 0 (Lipopolysaccharides); 0 (STAT6 Transcription Factor); 0 (Stat6 protein, mouse); 83652-28-2 (Calcitonin Gene-Related Peptide)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171120
[Lr] Data última revisão:
171120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE


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[PMID]:28817806
[Au] Autor:Ghitani N; Barik A; Szczot M; Thompson JH; Li C; Le Pichon CE; Krashes MJ; Chesler AT
[Ad] Endereço:National Center for Complementary and Integrative Health (NCCIH), National Institutes of Health (NIH), Bethesda MD, USA.
[Ti] Título:Specialized Mechanosensory Nociceptors Mediating Rapid Responses to Hair Pull.
[So] Source:Neuron;95(4):944-954.e4, 2017 Aug 16.
[Is] ISSN:1097-4199
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The somatosensory system provides animals with the ability to detect, distinguish, and respond to diverse thermal, mechanical, and irritating stimuli. While there has been progress in defining classes of neurons underlying temperature sensation and gentle touch, less is known about the neurons specific for mechanical pain. Here, we use in vivo functional imaging to identify a class of cutaneous sensory neurons that are selectively activated by high-threshold mechanical stimulation (HTMRs). We show that their optogenetic excitation evokes rapid protective and avoidance behaviors. Unlike other nociceptors, these HTMRs are fast-conducting Aδ-fibers with highly specialized circumferential endings wrapping the base of individual hair follicles. Notably, we find that Aδ-HTMRs innervate unique but overlapping fields and can be activated by stimuli as precise as the pulling of a single hair. Together, the distinctive features of this class of Aδ-HTMRs appear optimized for accurate and rapid localization of mechanical pain. VIDEO ABSTRACT.
[Mh] Termos MeSH primário: Vias Aferentes/fisiologia
Cabelo
Mecanorreceptores/fisiologia
Nociceptores/fisiologia
Células Receptoras Sensoriais/fisiologia
Tato/fisiologia
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Potenciais de Ação/fisiologia
Animais
Antineoplásicos Hormonais/farmacologia
Peptídeo Relacionado com Gene de Calcitonina/genética
Peptídeo Relacionado com Gene de Calcitonina/metabolismo
Channelrhodopsins
Diterpenos/farmacologia
Feminino
Cabelo/fisiologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Neurotoxinas/farmacologia
Pele/inervação
Canais de Cátion TRPV/genética
Canais de Cátion TRPV/metabolismo
Tamoxifeno/farmacologia
Gânglio Trigeminal/diagnóstico por imagem
Gânglio Trigeminal/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; VIDEO-AUDIO MEDIA
[Nm] Nome de substância:
0 (Antineoplastic Agents, Hormonal); 0 (Calca protein, mouse); 0 (Channelrhodopsins); 0 (Diterpenes); 0 (Neurotoxins); 0 (TRPV Cation Channels); 0 (TRPV1 protein, mouse); 094ZI81Y45 (Tamoxifen); 83652-28-2 (Calcitonin Gene-Related Peptide); A5O6P1UL4I (resiniferatoxin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE


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[PMID]:28792865
[Au] Autor:Charles A
[Ad] Endereço:From the UCLA Goldberg Migraine Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles.
[Ti] Título:Migraine.
[So] Source:N Engl J Med;377(6):553-561, 2017 Aug 10.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Transtornos de Enxaqueca/terapia
[Mh] Termos MeSH secundário: Anti-Inflamatórios não Esteroides/uso terapêutico
Antieméticos/uso terapêutico
Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores
Dieta
Feminino
Seres Humanos
Estilo de Vida
Transtornos de Enxaqueca/diagnóstico
Transtornos de Enxaqueca/etiologia
Neurotransmissores/uso terapêutico
Guias de Prática Clínica como Assunto
Triptaminas/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Antiemetics); 0 (Neurotransmitter Agents); 0 (Tryptamines); 83652-28-2 (Calcitonin Gene-Related Peptide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMcp1605502



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