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Calcitonin gene-related peptide

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https://www.readbyqxmd.com/read/28719042/serotonergic-paraneurons-in-the-female-mouse-urethral-epithelium-and-their-potential-role-in-peripheral-sensory-information-processing
#1
F Aura Kullmann, Huiyi H Chang, Christian Gauthier, Bronagh M McDonnell, Jih-Chao Yeh, Dennis R Clayton, Anthony J Kanai, William C de Groat, Gerard L Apodaca, Lori A Birder
AIM: The mechanisms underlying detection and transmission of sensory signals arising from visceral organs, such as the urethra, are poorly understood. Recently, specialized ACh-expressing cells embedded in the urethral epithelium have been proposed as chemosensory sentinels for detection of bacterial infection. Here we examined the morphology and potential role in sensory signaling of a different class of specialized cells that express serotonin (5-HT), termed paraneurons. METHODS: Urethrae, dorsal root ganglia neurons and spinal cords were isolated from adult female mice and used for immunohistochemistry and calcium imaging...
July 18, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28713981/neuroendocrine-factors-the-missing-link-in-non%C3%A2-melanoma-skin-cancer-review
#2
Mihai Lupu, Ana Caruntu, Constantin Caruntu, Laura Maria Lucia Papagheorghe, Mihaela Adriana Ilie, Vlad Voiculescu, Daniel Boda, Constantin Carolina, Cristiana Tanase, Maria Sifaki, Nikolaos Drakoulis, Charalampos Mamoulakis, George Tzanakakis, Monica Neagu, Demetrios A Spandidos, Boris N Izotov, Aristides M Tsatsakis
Non‑melanoma skin cancer (NMSC) is the most common form of cancer worldwide, comprising 95% of all cutaneous malignancies and approximately 40% of all cancers. In spite of intensive efforts aimed towards awareness campaigns and sun‑protective measures, epidemiological data indicate an increase in the incidence of NMSC. This category of skin cancers has many common environmental triggers. Arising primarily on sun‑exposed skin, it has been shown that ultraviolet radiation is, in the majority of cases, the main trigger involved in the pathogenesis of NMSC...
July 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28713051/3d-visualization-and-pathological-characteristics-of-cartilage-and-subchondral-bone-changes-in-the-lumbar-facet-joint-of-an-ovariectomized-mouse-model
#3
Yong Cao, Shuangfei Ni, Tianding Wu, Chunyue Duan, Shenghui Liao, Jianzhong Hu
BACKGROUD CONTEXT: Low back pain (LBP) is more prevalent among postmenopausal women than men. Ovariectomy (OVX) is an established animal model that mimics the estrogen deficiency of postmenopausal women. Little is known about the morphological properties of cartilage and subchondral bone changes in the lumbar facet joint (LFJ) of an OVX mouse model. PURPOSE: The purpose of this study is to characterize the morphological change of cartilage and subchondral bone in LFJ of an OVX mouse model...
July 13, 2017: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/28707585/migraine-neurogenic-inflammation-drug-development-pharmacochemical-aspects
#4
Melinda Lukács, János Tajti, Ferenc Fülöp, József Toldi, Lars Edvinsson, László Vécsei
BACKGROUND: Migraine is a primary headache disorder. Despite numerous studies conducted with the aim to understand the pathophysiology of migraine, several aspects are still unclear. The trigeminovascular system plays a key role. Neurogenic inflammation is presumed to be an important factor in migraine pathophysiology, mediated by the activation of primary neurons, leading to the release of various pro-inflammatory neuropeptides and neurotransmitters such as Calcitonin Gene-Related Peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP)...
July 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28706220/opportunities-for-therapeutic-antibodies-directed-at-g-protein-coupled-receptors
#5
REVIEW
Catherine J Hutchings, Markus Koglin, William C Olson, Fiona H Marshall
G-protein-coupled receptors (GPCRs) are activated by a diverse range of ligands, from large proteins and proteases to small peptides, metabolites, neurotransmitters and ions. They are expressed on all cells in the body and have key roles in physiology and homeostasis. As such, GPCRs are one of the most important target classes for therapeutic drug discovery. The development of drugs targeting GPCRs has therapeutic value across a wide range of diseases, including cancer, immune and inflammatory disorders as well as neurological and metabolic diseases...
July 14, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28705807/augmentation-of-cgmp-pkg-pathway-and-colonic-motility-by-hydrogen-sulfide
#6
Ancy D Nalli, Sayak Bhattacharya, Hongxia Wang, Derek M Kendig, John R Grider, Karnam S Murthy
Hydrogen sulfide (H2S), like nitric oxide (NO), causes smooth muscle relaxation, but unlike NO, does not stimulate soluble guanylyl cyclase (sGC) activity and generate cGMP. The aim of this study was to investigate the interplay between NO and H2S in colonic smooth muscle. In colonic smooth muscle from rabbit, mouse and human, L-cysteine, substrate of cystathionine-γ-lyase (CSE), or NaHS, an H2S donor, inhibited phosphodiesterase 5 (PDE5) activity and augmented the increase in cGMP levels, IP3 receptor phosphorylation at Ser(1756) (measured as a proxy for PKG activation), and muscle relaxation in response to NO donor, s-nitrosoglutathione (GSNO), suggesting augmentation of cGMP/PKG pathway by H2S...
July 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28705698/receptor-activity-modifying-protein-dependent-and-independent-activation-mechanisms-in-the-coupling-of-calcitonin-gene-related-peptide-and-adrenomedullin-receptors-to-gs
#7
Michael J Woolley, Christopher A Reynolds, John Simms, Christopher S Walker, Juan Carlos Mobarec, Michael L Garelja, Alex C Conner, David R Poyner, Debbie L Hay
Calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) receptors are heteromers of the calcitonin receptor-like receptor (CLR), a class B G protein-coupled receptor, and one of three receptor activity-modifying proteins (RAMPs). How CGRP and AM activate CLR and how this process is modulated by RAMPs is unclear. We have defined how CGRP and AM induce Gs-coupling in CLR-RAMP heteromers by measuring the effect of targeted mutagenesis in the CLR transmembrane domain on cAMP production, modeling the active state conformations of CGRP and AM receptors in complex with the Gs C-terminus and conducting molecular dynamics simulations in an explicitly hydrated lipidic bilayer...
July 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28701511/n-arachidonoyl-dopamine-modulates-acute-systemic-inflammation-via-nonhematopoietic-trpv1
#8
Samira K Lawton, Fengyun Xu, Alphonso Tran, Erika Wong, Arun Prakash, Mark Schumacher, Judith Hellman, Kevin Wilhelmsen
N-Arachidonoyl dopamine (NADA) is an endogenous lipid that potently activates the transient receptor potential vanilloid 1 (TRPV1), which mediates pain and thermosensation. NADA is also an agonist of cannabinoid receptors 1 and 2. We have reported that NADA reduces the activation of cultured human endothelial cells by LPS and TNF-α. Thus far, in vivo studies using NADA have focused on its neurologic and behavioral roles. In this article, we show that NADA potently decreases in vivo systemic inflammatory responses and levels of the coagulation intermediary plasminogen activator inhibitor 1 in three mouse models of inflammation: LPS, bacterial lipopeptide, and polymicrobial intra-abdominal sepsis...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28700339/trypsin-protease-activated-receptor-2-signaling-contributes-to-pancreatic-cancer-pain
#9
Jiao Zhu, Xue-Rong Miao, Kun-Ming Tao, Hai Zhu, Zhi-Yun Liu, Da-Wei Yu, Qian-Bo Chen, Hai-Bo Qiu, Zhi-Jie Lu
Pain treatment is a critical aspect of pancreatic cancer patient clinical care. This study investigated the role of trypsin-protease activated receptor-2 (PAR-2) in pancreatic cancer pain. Pancreatic tissue samples were collected from pancreatic cancer (n=22) and control patients (n=22). Immunofluorescence analyses confirmed colocalization of PAR-2 and neuronal markers in pancreatic cancer tissues. Trypsin levels and protease activities were higher in pancreatic cancer tissue specimens than in the controls...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28697491/trpc1-trpc3-and-trpc4-in-rat-orofacial-structures
#10
Masatoshi Fujita, Tadasu Sato, Takehiro Yajima, Eiji Masaki, Hiroyuki Ichikawa
TRPC (transient receptor potential cation channel subfamily C) members are nonselective monovalent cation channels and control Ca2+ inflow. In this study, immunohistochemistry for TRPC1, TRPC3, and TRPC4 was performed on rat oral and craniofacial structures to elucidate their distribution and function in the peripheries. In the trigeminal ganglion (TG), 56.1, 84.1, and 68.3% of sensory neurons were immunoreactive (IR) for TRPC1, TRPC3, and TRPC4, respectively. A double immunofluorescence method revealed that small to medium-sized TG neurons co-expressed TRPCs and calcitonin gene-related peptide...
July 12, 2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28695626/mucosal-glucagon-like-peptide-1-glp-1-responses-are-mediated-by-calcitonin-gene-related-peptide-cgrp-in-the-mouse-colon-and-both-peptide-responses-are-area-specific
#11
I R Tough, R Moodaley, H M Cox
BACKGROUND: Glucagon-like peptide (GLP)-1 is an incretin hormone and its mimetics are proven antidiabetic and antiobesity drugs. GLP-1 exerts antimotility and mucosal proliferative activities but its epithelial ion transport effects are uncharacterized and these may contribute to the gastrointestinal (GI) disturbance, i.e., diarrhea experienced with some GLP-1 mimetics. Our aim was to establish GLP-1 agonist mechanisms and identify potential mucosal mediator(s) in the colonic tissue from C57BL/6J mice...
July 11, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28694067/pharmacological-analysis-of-the-inhibition-produced-by-moxonidine-and-agmatine-on-the-vasodepressor-sensory-cgrpergic-outflow-in-pithed-rats
#12
Eloísa Rubio-Beltrán, Alejandro Labastida-Ramírez, Oswaldo Hernández-Abreu, Antoinette MaassenVanDenBrink, Carlos M Villalón
Calcitonin gene-related peptide (CGRP) plays a role in several (patho)physiological functions, and modulation of its release is considered a therapeutic target. In this respect, electrical spinal (T9-T12) stimulation of the perivascular sensory outflow in pithed rats produces vasodepressor responses mediated by CGRP release. This study investigated the role of imidazoline I1 and I2 receptors in the inhibition by moxonidine and agmatine of these vasodepressor responses. Male Wistar pithed rats (pretreated i...
July 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28691801/relative-antagonism-of-mutants-of-the-cgrp-receptor-extracellular-loop-2-domain-ecl2-using-a-truncated-competitive-antagonist-cgrp8-37-evidence-for-the-dual-involvement-of-ecl2-in-the-two-domain-binding-model
#13
Michael J Woolley, John Simms, Sifat Uddin, David R Poyner, Alex C Conner
The second extracellular loop (ECL2) of the G protein-coupled receptor (GPCR) family is important for ligand interaction and drug discovery. ECL2 of the family B cardioprotective calcitonin gene-related peptide (CGRP) receptor is required for cell signaling. Family B GPCR ligands have two regions; the N-terminus mediates receptor activation, and the remainder confers high-affinity binding. Comparing antagonism of CGRP8-37 at a number of point mutations of ECL2 of the CGRP receptor, we show that the ECL2 potentially facilitates interaction with up to the 18 N-terminal residues of CGRP...
July 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28689049/the-spatiotemporal-relationships-between-chondroitin-sulfate-proteoglycans-and-terminations-of-calcitonin-gene-related-peptide-and-parvalbumin-immunoreactive-afferents-in-the-spinal-cord-of-mouse-embryos
#14
Liqing Wang, Chao Yu, Jun Wang, Hui Zhao, Sun-On Chan
Chondroitin sulfate (CS) proteoglycans (PGs) are a family of complex molecules in the extracellular matrix and cell surface that regulate axon growth and guidance during development of the central nervous system. In this study, the expression of CSPGs was investigated in the mouse spinal cord at late embryonic and neonatal stages using CS-56 antibody. CS immunoreactivity was observed abundantly in ventral regions of spinal cord of embryonic day (E) 15 embryos. At E16 to E18, CS expression spread dorsally, but never reached the superficial layers of the dorsal horn...
July 5, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28687197/opioid-receptor-activation-is-involved-in-neuroprotection-induced-by-trpv1-channel-activation-against-excitotoxicity-in-the-rat-retina
#15
Kenji Sakamoto, Taiyo Kuroki, Tomonori Sagawa, Hiroko Ito, Asami Mori, Tsutomu Nakahara, Kunio Ishii
Recently, we reported that capsaicin, a transient receptor potential vanilloid type1 (TRPV1) agonist, protected against excitotoxicity induced by intravitreal N-methyl-D-aspartic acid (NMDA) in the rats in vivo. It has been reported that morphine, an opioid receptor agonist, ameliorated excitotoxicity induced by ischemia-reperfusion in the retina, and that capsaicin-induced neuroprotection was reduced by naloxone, an opioid receptor antagonist in the brain. The aim of the present study is to clarify whether activation of opioid receptors is involved in the capsaicin-induced neuroprotection in the retina...
July 4, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28682541/-effect-of-calcitonin-gene-related-peptide-on-mc3t3-e1-osteoblast-apoptosis-and-autophagy-induced-by-serum-starvation
#16
An Yang, Zhang Huiyu, Guo Junfeng, Li Xin, Yang Yang, Zhang Gang, Tan Yinghui
OBJECTIVE: To study the effect of calcitonin gene-related peptide (CGRP) on apoptosis and autophagy of mouse MC3T3-E1 osteoblast and their interaction and to further clarify protective mechanism of CGRP on osteoblasts. METHODS: MC3T3-E1 osteoblasts of mouse were cultured in vitro. Western blot and flow cytometry were used to detect expressions of microtubule-associated protein 1 light chain 3 (LC3) and P62 protein of MC3T3-E1 osteoblasts cultured with serum culture and serum-free (serum starvation) culture...
April 1, 2017: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/28679347/serotonin-calcitonin-and-calcitonin-gene-related-peptide-in-acute-pancreatitis
#17
Kirsten Lykke Wahlstrøm, Srdan Novovic, Annette Kjær Ersbøll, Philip Hasbak, Lars Nannestad Jørgensen, Mark Berner Hansen
OBJECTIVE: The aim of this study was to investigate plasma levels of serotonin, calcitonin and calcitonin gene-related peptide (CGRP) in the course of acute pancreatitis (AP) taking organ failure, etiology and severity into consideration. MATERIAL AND METHODS: Sixty consecutive patients with alcohol- or gallstone-induced AP were included over a 15-month period. Patients were treated according to a standardized algorithm and monitored for organ specific morbidity and mortality...
July 5, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28671709/transient-receptor-potential-a1-trpa1-agonists-inhibit-contractions-of-the-isolated-human-ureter
#18
Philipp Weinhold, Martin Hennenberg, Frank Strittmatter, Christian G Stief, Christian Gratzke, Petter Hedlund
AIMS: Mechanoafferent and peristaltic mechanisms of the human ureter involve transient receptor potential V1 (TRPV1)- and purinoceptor-mediated functions. Hydrogen sulphide, an endogenous TRPA1 ligand, is linked to inhibitory neurotransmission of the pig ureter. No information is available on TRPA1 activity in the human ureter. We therefore examined the distribution and function of TRPA1 in the human ureter. METHODS: Expression of TRPA1 in human ureter tissue was studied by Western blot and immunofluorescence...
July 3, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28666011/differential-effects-of-calca-derived-peptides-in-male-mice-with-diet-induced-obesity
#19
Alexander Bartelt, Anke Jeschke, Brigitte Müller, Isabella Gaziano, Michelle Morales, Timur Yorgan, Timo Heckt, Markus Heine, Robert F Gagel, Ronald B Emeson, Michael Amling, Andreas Niemeier, Jörg Heeren, Thorsten Schinke, Johannes Keller
Key metabolic hormones, such as insulin, leptin, and adiponectin, have been studied extensively in obesity, however the pathophysiologic relevance of the calcitonin family of peptides remains unclear. This family includes calcitonin (CT), its precursor procalcitonin (PCT), and alpha calcitonin-gene related peptide (αCGRP), which are all encoded by the gene Calca. Here, we studied the role of Calca-derived peptides in diet-induced obesity (DIO) by challenging Calcr-/- (encoding the calcitonin receptor, CTR), Calca-/-, and αCGRP-/- mice and their respective littermates with high-fat diet (HFD) feeding for 16 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28660990/-venopunction-of-the-cubital-vein-as-an-alternative-approach-for-cgrp-plasma-level-evaluation-in-tmd-patients
#20
Aleksandra Nitecka-Buchta, Bogdan Marek, Jolanta Batko Kapustecka, Stefan Baron
INTRODUCTION: Calcitonin gene-related peptide is an important vasodilator. It plays an important role in the metabolism of chewing muscles. The aim of the study was to evaluate the plasma level of CGRP in patients with myofascial pain (RDC/TMD Ia) and myofascial pain with limited opening (RDC/TMD Ib) before and after occlusal splint therapy (Michigan splint). MATERIAL AND METHODS: A randomised trial was performed including 39 patients (males = 3, females = 36). Blood samples were taken from the external jugular vein (JUG) and cubital vein (CUB) before and after 30 days of occlusal splint therapy...
2017: Endokrynologia Polska
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