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Calcitonin gene-related peptide

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https://www.readbyqxmd.com/read/28792272/trigeminovascular-calcitonin-gene-related-peptide-function-in-cacna1a-r192q-mutated-knock-in-mice
#1
Kayi Y Chan, Alejandro Labastida-Ramírez, Martha B Ramírez-Rosas, Sieneke Labruijere, Ingrid M Garrelds, Alexander Hj Danser, Arn Mjm van den Maagdenberg, Antoinette MaassenVanDenBrink
Familial hemiplegic migraine type 1 (FHM1) is a rare migraine subtype. Whereas transgenic knock-in mice with the human pathogenic FHM1 R192Q missense mutation in the Cacna1a gene reveal overall neuronal hyperexcitability, the effects on the trigeminovascular system and calcitonin gene-related peptide (CGRP) receptor are largely unknown. This gains relevance as blockade of CGRP and its receptor are therapeutic targets under development. Hence, we set out to test these effects in FHM1 mice. We characterized the trigeminovascular system of wild-type and FHM1 mice through: (i) in vivo capsaicin- and CGRP-induced dural vasodilation in a closed-cranial window; (ii) ex vivo KCl-induced CGRP release from isolated dura mater, trigeminal ganglion and trigeminal nucleus caudalis; and (iii) peripheral vascular function in vitro ...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28790969/alpha-calcitonin-gene-related-peptide-increases-cerebral-vessel-diameter-in-animal-models-of-subarachnoid-hemorrhage-a-systematic-review-and-meta-analysis
#2
REVIEW
Liam M C Flynn, Caroline J Begg, Malcolm R Macleod, Peter J D Andrews
Delayed cerebral ischemia (DCI) is a life-threatening complication after subarachnoid hemorrhage. There is a strong association between cerebral vessel narrowing and DCI. Alpha calcitonin gene-related peptide (αCGRP) is a potent vasodilator, which may be effective at reducing cerebral vessel narrowing after subarachnoid hemorrhage (SAH). Here, we report a meta-analysis of data from nine in vivo animal studies identified in a systematic review in which αCGRP was administered in SAH models. Our primary outcome was change in cerebral vessel diameter and the secondary outcome was change in neurobehavioral scores...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28769868/hydrogen-sulfide-mediating-both-excitatory-and-inhibitory-effects-in-a-rat-model-of-meningeal-nociception-and-headache-generation
#3
Christiane Teicher, Roberto De Col, Karl Messlinger
BACKGROUND/PURPOSE: Hydrogen sulfide (H2S) is a neuromodulator acting through nitroxyl (HNO) when it reacts with nitric oxide (NO). HNO activates transient receptor potential channels of the ankyrin type 1 (TRPA1) causing release of calcitonin gene-related peptide from primary afferents. Activation of meningeal nociceptors projecting to the human spinal trigeminal nucleus (STN) may lead to headaches. In a rat model of meningeal nociception, the activity of spinal trigeminal neurons was used as read-out for the interaction between H2S and NO...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28767512/dissecting-the-role-of-the-crmp2-neurofibromin-complex-on-pain-behaviors
#4
Aubin Moutal, Yue Wang, Xiaofang Yang, Yingshi Ji, Shizhen Luo, Angie Dorame, Shreya S Bellampalli, Lindsey A Chew, Song Cai, Erik T Dustrude, James E Keener, Michael T Marty, Todd W Vanderah, Rajesh Khanna
Neurofibromatosis type 1 (NF1), a genetic disorder linked to inactivating mutations or homozygous deletion of the Nf1 gene, is characterized by tumorigenesis, cognitive dysfunction, seizures, migraine, and pain. Omic studies on human NF1 tissues identified an increase in expression of collapsin response mediator protein 2 (CRMP2), a cytosolic protein reported to regulate the trafficking and activity of presynaptic N-type voltage-gated calcium (Cav2.2) channels. Since neurofibromin, the protein product of the Nf1 gene, binds to and inhibits CRMP2, the neurofibromin-CRMP2 signaling cascade will likely affect Ca2+ channel activity and regulate nociceptive neurotransmission and in vivo responses to noxious stimulation...
July 31, 2017: Pain
https://www.readbyqxmd.com/read/28760938/vasorelaxation-to-the-nitroxyl-donor-isopropylamine-nonoate-in-resistance-arteries-does-not-require-perivascular-calcitonin-gene-related-peptide
#5
Alice M H Pinkney, Hamish A L Lemmey, Kim A Dora, Christopher J Garland
Nitroxyl (HNO) donors offer considerable therapeutic potential for the treatment of hypertension-related cardiovascular disorders, particularly heart failure, as they combine an inotropic action with peripheral vasodilation. Angeli's salt is the only HNO donor whose mechanism has been studied in depth, and recently, Angeli's salt vasodilation was suggested to be indirect and caused by calcitonin gene-related peptide (CGRP) released from perivascular nerves after HNO activates TRPA1 (transient receptor potential cation channel subfamily A member 1) channels...
July 31, 2017: Hypertension
https://www.readbyqxmd.com/read/28756217/maternal-insulin-therapy-does-not-restore-foetoplacental-endothelial-dysfunction-in-gestational-diabetes-mellitus
#6
Mario Subiabre, Luis Silva, Roberto Villalobos-Labra, Fernando Toledo, Mario Paublo, Marcia A López, Rocío Salsoso, Fabián Pardo, Andrea Leiva, Luis Sobrevia
Pregnant women diagnosed with gestational diabetes mellitus subjected to diet (GDMd) that do not reach normal glycaemia are passed to insulin therapy (GDMi). GDMd associates with increased human cationic amino acid transporter 1 (hCAT-1)-mediated transport of L-arginine and nitric oxide synthase (NOS) activity in foetoplacental vasculature, a phenomenon reversed by exogenous insulin. Whether insulin therapy results in reversal of the GDMd effect on the foetoplacental vasculature is unknown. We assayed whether insulin therapy normalizes GDMd-associated foetoplacental endothelial dysfunction...
July 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28754314/the-role-of-celsr3-in-the-development-of-central-somatosensory-projections-from-dorsal-root-ganglia
#7
Feifei Wang, Qianghua Wang, Chen Li, Panpan Yu, Yibo Qu, Libing Zhou
Dorsal root ganglion (DRG) neurons receive peripheral somatosensory information and send orderly projections to second-order relay nuclei in the spinal cord and in the brainstem. Atypical cadherin Celsr3 is known to play a critical role in wiring of several central and peripheral axons. Although Celsr3 mRNA is heavily expressed in DRG neurons, its role in the development of somatosensory projections remains unexplored. Here we assessed the role of Celsr3 in DRG using conditional gene inactivation in crosses with Wnt1-Cre mice...
July 25, 2017: Neuroscience
https://www.readbyqxmd.com/read/28742111/axonal-outgrowth-neuropeptides-expression-and-receptors-tyrosine-kinase-phosphorylation-in-3d-organotypic-cultures-of-adult-dorsal-root-ganglia
#8
Estrela Neto, Cecília J Alves, Luís Leitão, Daniela M Sousa, Inês S Alencastre, Francisco Conceição, Meriem Lamghari
Limited knowledge from mechanistic studies on adult sensory neuronal activity was generated, to some extent, in recapitulated adult in vivo 3D microenvironment. To fill this gap there is a real need to better characterize the adult dorsal root ganglia (aDRG) organotypic cultures to make these in vitro systems exploitable for different approaches, ranging from basic neurobiology to regenerative therapies, to address the sensory nervous system in adult stage. We conducted a direct head-to-head comparison of aDRG and embryonic DRG (eDRG) organotypic culture focusing on axonal growth, neuropeptides expression and receptors tyrosine kinase (RTK) activation associated with neuronal survival, proliferation and differentiation...
2017: PloS One
https://www.readbyqxmd.com/read/28739811/calcitonin-gene-related-peptide-receptor-agonism-a-double-edged-sword
#9
EDITORIAL
A H Jan Danser, Antoinette MaassenVanDenBrink
No abstract text is available yet for this article.
July 25, 2017: Circulation
https://www.readbyqxmd.com/read/28738112/central-role-of-protein-kinase-a-in-promoting-trigeminal-nociception-in-an-in-vivo-model-of-temporomandibular-disorders
#10
Lindsey K Koop, Jordan L Hawkins, Lauren E Cornelison, Paul L Durham
AIMS: To investigate cellular changes in the spinal trigeminal nucleus (STN) and trigeminal ganglion (TG) associated with trigeminal nociception mediated by inflammation in the temporomandibular joint (TMJ). METHODS: Male Sprague-Dawley rats (n = 86) were utilized to investigate cellular and behavioral responses to prolonged TMJ inflammation caused by bilateral injection of Complete Freund's Adjuvant (CFA) in the TMJ capsules. To investigate the cellular effects of protein kinase A (PKA) in the STN, rats were injected intrathecally with the selective PKA inhibitor KT5720 prior to injection of CFA into both TMJ capsules...
July 2017: Journal of Oral & Facial Pain and Headache
https://www.readbyqxmd.com/read/28736918/phase-1-randomized-double-blind-placebo-controlled-single-dose-and-multiple-dose-studies-of-erenumab-in-healthy-subjects-and-patients-with-migraine
#11
Jan de Hoon, Anne Van Hecken, Corinne Vandermeulen, Lucy Yan, Brian Smith, Jiyun Sunny Chen, Edgar Bautista, Lisa Hamilton, Javier Waksman, Thuy Vu, Gabriel Vargas
Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) signaling are being explored as prophylactic treatments for migraine. Erenumab (AMG 334) is the first potent, selective, and competitive human mAb antagonist of the CGRP receptor. We report the data from two phase 1 studies assessing the safety, pharmacokinetics (PK), and pharmacodynamics of single and multiple administrations of erenumab in healthy subjects and patients with migraine. The results indicate that the PK profile of erenumab is nonlinear from 1 mg to 70 mg and the linear portion of the clearance from 70 mg to 210 mg is consistent with other human immunoglobulin (Ig)G2 antibodies...
July 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28734832/superficial-esophageal-mucosal-afferent-nerves-may-contribute-to-reflux-hypersensitivity-in-non-erosive-reflux-disease
#12
P Woodland, J L Ooi, F Grassi, K Nikaki, C Lee, J A Evans, N Koukias, C Triantos, S A McDonald, M Peiris, R Aktar, L A Blackshaw, D Sifrim
BACKGROUND & AIMS: Little is known about the causes of heartburn in patients with gastro-esophageal reflux disease (GERD). Visible epithelial damage is seldom associated with symptom severity, evidenced by the significant symptom burden in patients with non-erosive reflux disease (NERD) compared to patients with erosive reflux disease (ERD) or Barrett's esophagus (BE). We studied the distribution of mucosal nerve fibers in patients with NERD, ERD, and BE, and compared the results with those of healthy subjects...
July 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28731365/chemical-composition-and-antimigraine-activity-of-essential-oil-of-angelicae-dahuricae-radix
#13
Jingbo Sun, He Li, Jinghui Sun, Huimin Liu, Jianguang Chen, Chunmei Wang
The aim of this study was to explore the chemical composition and the effect of essential oil of Angelicae dahuricae radix on a nitroglycerin (NTG)-induced rat model of migraine. The CO2 supercritical fluid extraction method was optimized for the extraction of essential oil of A. dahuricae radix (EOAD) and its chemical composition was determined. The migraine model was established by subcutaneous injection of NTG (10 mg/kg) 1 h after the last administration of EOAD. The therapeutic effect of EOAD and its underlying mechanism were assessed by monitoring behavioral changes, levels of nitric oxide (NO) in serum and brain tissues, plasma levels of calcitonin gene-related peptide (CGRP) and endothelin (ET), and ET/NO ratio...
August 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28730896/cannabinoid-hyperemesis-syndrome-potential-mechanisms-for-the-benefit-of-capsaicin-and-hot-water-hydrotherapy-in-treatment
#14
John R Richards, Jeff M Lapoint, Guillermo Burillo-Putze
INTRODUCTION: Cannabinoid hyperemesis syndrome is a clinical disorder that has become more prevalent with increasing use of cannabis and synthetic cannabinoids, and which is difficult to treat. Standard antiemetics commonly fail to alleviate the severe nausea and vomiting characteristic of the syndrome. Curiously, cannabinoid hyperemesis syndrome patients often report dramatic relief of symptoms with hot showers and baths, and topical capsaicin. OBJECTIVES: In this review, we detail the pharmacokinetics and pharmacodynamics of capsaicin and explore possible mechanisms for its beneficial effect, including activation of transient receptor potential vanilloid 1 and neurohumoral regulation...
July 21, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28727763/loss-of-receptor-activity-modifying-protein-2-in-mice-causes-placental-dysfunction-and-alters-pth1r-regulation
#15
Mahita Kadmiel, Brooke C Matson, Scott T Espenschied, Patricia M Lenhart, Kathleen M Caron
Receptor activity-modifying protein 2 (Ramp2) is a single-pass transmembrane protein that heterodimerizes with several family B G-protein coupled receptors to alter their function. Ramp2 has been primarily characterized in association with calcitonin receptor-like receptor (Calcrl, CLR), forming the canonical receptor complex for the endocrine peptide adrenomedullin (Adm, AM). However, we previously demonstrated that Ramp2+/- female mice display a constellation of endocrine-related phenotypes that are distinct from those of Adm+/- and Calcrl+/- mice, implying that RAMP2 has physiological functions beyond its canonical complex...
2017: PloS One
https://www.readbyqxmd.com/read/28726232/-frequent-episodic-migraine-and-calcitonin-gene-related-peptide-influence-of-treatment-with-topiramate-and-zonisamide-on-levels-of-the-peptide
#16
D A Garcia-Estevez, M Pardo-Parrado, S Silvarrey-Rodriguez
INTRODUCTION: The pathophysiology of pain in migraine is related to the activation of the trigeminovascular system by releasing vasoactive neuropeptides, the most important of which is calcitonin gene-related peptide (CGRP), which causes a neurogenic inflammation in the leptomeningeal vessels. AIM: To study whether CGRP is increased in frequent episodic migraine and whether preventive treatment with topiramate or zonisamide modifies its levels. SUBJECTS AND METHODS: We studied 28 patients with episodic migraine with or without aura, in accordance with the International Headache Society criteria, with a frequency of 4-14 days/month...
August 16, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28719042/serotonergic-paraneurons-in-the-female-mouse-urethral-epithelium-and-their-potential-role-in-peripheral-sensory-information-processing
#17
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
#18
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
#19
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
#20
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
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