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Charles E Norton, Steven S Segal
The sensory neurotransmitter calcitonin gene-related peptide (CGRP) is associated with vasodilation of systemic arteries through activation of ATP-sensitive potassium channels (KATP) in smooth muscle cells (SMCs), however its effects on endothelial cell (EC) membrane potential (Vm) are unresolved. In pulmonary arteries (PAs) of C57BL/6J mice, we questioned whether CGRP would hyperpolarize ECs as well as SMCs. Intact PAs were isolated and immunostained for CGRP to confirm sensory innervation; vessel segments (length, 1-2 mm; diameter ∼150 µm) with intact or denuded endothelium were cannulated and pressurized to 16 cm H2O at 37{degree sign}C...
March 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Antonietta Messina, Ilaria Bitetti, Francesco Precenzano, Diego Iacono, Giovanni Messina, Michele Roccella, Lucia Parisi, Margherita Salerno, Anna Valenzano, Agata Maltese, Monica Salerno, Francesco Sessa, Giuseppe Davide Albano, Rosa Marotta, Ines Villano, Gabriella Marsala, Christian Zammit, Francesco Lavano, Marcellino Monda, Giuseppe Cibelli, Serena Marianna Lavano, Beatrice Gallai, Roberto Toraldo, Vincenzo Monda, Marco Carotenuto
Introduction: Sleep and migraine share a common pathophysiological substrate, although the underlying mechanisms are unknown. The serotonergic and orexinergic systems are both involved in the regulation of sleep/wake cycle, and numerous studies show that both are involved in the migraine etiopathogenesis. These two systems are anatomically and functionally interconnected. Our hypothesis is that in migraine a dysfunction of orexinergic projections on the median raphe (MR) nuclei, interfering with serotonergic regulation, may cause Non-Rapid Eye Movement parasomnias, such as somnambulism...
2018: Frontiers in Neurology
Satyanarayana Achanta, Narendranath Reddy Chintagari, Marian Brackmann, Shrilatha Balakrishna, Sven-Eric Jordt
The skin is highly sensitive to the chemical warfare agent in mustard gas, sulfur mustard (SM) that initiates a delayed injury response characterized by erythema, inflammation and severe vesication (blistering). Although SM poses a continuing threat, used as recently as in the Syrian conflict, no mechanism-based antidotes against SM are available. Recent studies demonstrated that Transient Receptor Potential Ankyrin 1 (TRPA1), a chemosensory cation channel in sensory nerves innervating the skin, is activated by SM and 2-chloroethyl ethyl sulfide (CEES), an SM analog, in vitro, suggesting it may promote vesicant injury...
March 10, 2018: Toxicology Letters
Karl Messlinger
BACKGROUND: Calcitonin gene-related peptide (CGRP) has long been a focus of migraine research, since it turned out that inhibition of CGRP or CGRP receptors by antagonists or monoclonal IgG antibodies was therapeutic in frequent and chronic migraine. This contribution deals with the questions, from which sites CGRP is released, where it is drained and where it acts to cause its headache proliferating effects in the trigeminovascular system. RESULTS: The available literature suggests that the bulk of CGRP is released from trigeminal afferents both in meningeal tissues and at the first synapse in the spinal trigeminal nucleus...
March 12, 2018: Journal of Headache and Pain
Lars Edvinsson, János Tajti, Levente Szalárdy, László Vécsei
Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide implicated in a wide range of functions, such as nociception and in primary headaches. Regarding its localization, PACAP has been observed in the sensory trigeminal ganglion (TG), in the parasympathetic sphenopalatine (SPG) and otic ganglia (OTG), and in the brainstem trigeminocervical complex. Immunohistochemistry has shown PACAP-38 in numerous cell bodies of SPG/OTG, co-stored with vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS) and, to a minor degree, with choline acetyltransferase...
March 9, 2018: Journal of Headache and Pain
Yuan Li, Huiping Zhang, Yi Liang, Wei Wang, Tongshun Xu, Jifang Zhang, Wenliang Xiao, Tao Wang
BACKGROUND: To improve therapy for slow coronary flow (SCF), the effects of hyperbaric oxygen (HBO) therapy on vascular endothelial function in SCF patients is the focus of this investigation. METHODS: Ninety-eight patients who exhibited chest discomfort were retrospectively analyzed, and di-agnosed with SCF by coronary artery angiography at the Third Hospital of Hebei Medical University, Shijiazhuang, China from 2014 to 2016. The patients were divided into two groups according to the following treatment: HBO group (n = 48) and the control group (n = 50)...
2018: Cardiology Journal
Aneta Stefanidis, Nicole M Wiedmann, Sonika Tyagi, Andrew M Allen, Matthew J Watt, Brian J Oldfield
OBJECTIVE: The potential for brown adipose tissue (BAT) to be targeted as a therapeutic option to combat obesity has been heightened by the discovery of a brown-like form of inducible "beige" adipose tissue in white fat which has overlapping structural and functional properties to "classical" BAT. The likelihood that both beige and brown fat are recruited functionally by neural mechanisms, taken together with the lack of a detailed understanding of the nature of changes in the nervous system when white adipose tissue (WAT) is transformed to brown, provides the impetus for this study...
February 10, 2018: Molecular Metabolism
Pankaj Baral, Benjamin D Umans, Lu Li, Antonia Wallrapp, Meghna Bist, Talia Kirschbaum, Yibing Wei, Yan Zhou, Vijay K Kuchroo, Patrick R Burkett, Bryan G Yipp, Stephen D Liberles, Isaac M Chiu
Lung-innervating nociceptor sensory neurons detect noxious or harmful stimuli and consequently protect organisms by mediating coughing, pain, and bronchoconstriction. However, the role of sensory neurons in pulmonary host defense is unclear. Here, we found that TRPV1+ nociceptors suppressed protective immunity against lethal Staphylococcus aureus pneumonia. Targeted TRPV1+ -neuron ablation increased survival, cytokine induction, and lung bacterial clearance. Nociceptors suppressed the recruitment and surveillance of neutrophils, and altered lung γδ T cell numbers, which are necessary for immunity...
March 5, 2018: Nature Medicine
Paraskevi L Tsiolaki, Georgia I Nasi, Fotis A Baltoumas, Nikolaos N Louros, Vassiliki Magafa, Stavros J Hamodrakas, Vassiliki A Iconomidou
The Calcitonin-gene related peptide (CGRP) family is a group of peptide hormones, which consists of IAPP, calcitonin, adrenomedullin, intermedin, αCGRP and βCGRP. IAPP and calcitonin have been extensively associated with the formation of amyloid fibrils, causing Type 2 Diabetes and Medullary Thyroid Carcinoma, respectively. In contrast, the potential amyloidogenic properties of αCGRP still remain unexplored, although experimental trials have indicated its presence in deposits, associated with the aforementioned disorders...
March 1, 2018: Journal of Structural Biology
D N Luo, F J Li, Y Y Zou
Objective: To determine the therapic effects of rutaecarpine in dextran sodium sulfate (DSS)induced experimental colitis and explore whether the protective role of rutaecarpine is related to the synthesis and release of CGRP. Methods: Fifty female BABL/c strain mice were randomly divided into untreated model control group and DSS-exposed groups.DSS-exposed groups were given administration of 5% DSS for 7 days and respectively treated with vehicle, rutacarpine(30 mg/kg, 100 mg/kg) , prednisone by intragastric administration from day 8 to day 14...
February 13, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Xin Wu, Wan-Jun Zheng, Ming-Hui Lv, Shao-Hua Su, Song-Jiang Zhang, Jian-Feng Gao
The purpose of this study was to explore the effects of different concentrations of calcitonin gene-related peptide (CGRP) on long-term potentiation (LTP) in the hippocampus of mice. C57BL/6J mice (30 days old) were randomly divided into control group, three CGRP groups, and CGRP + CGRP8-37 group (10 mice for each group). Different concentrations of CGRP (50, 100 and 200 nmol/L) were given to the hippocampal slices of mice. The presynaptic release of neurotransmitters and the induction of LTP were measured by extracellular field recording techniques...
February 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Jason A Bleedorn, Troy A Hornberger, Craig A Goodman, Zhengling Hao, Susannah J Sample, Ermias Amene, Mark D Markel, Mary Behan, Peter Muir
Mechanical signals play an integral role in the regulation of bone mass and functional adaptation to bone loading. The osteocyte has long been considered the principle mechanosensory cell type in bone, although recent evidence suggests the sensory nervous system may play a role in mechanosensing. The specific signaling pathways responsible for functional adaptation of the skeleton through modeling and remodeling are not clearly defined. In vitro studies suggest involvement of intracellular signaling through mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and mammalian target of rapamycin (mTOR)...
2018: PloS One
Jianxiong Hu, Wei Lin, Chengfei Zhao, Jianfang Chen
BACKGROUND: Activation of trypsin from proteolytic cleavage of trypsinogen in the pancreas can lead to acute pancreatitis. Calcitonin gene related peptide (CGRP) from both peripheral and central neurons is involved in a variety of physiological/pathophysiological processes, especially sensory (nociceptive) and efferent (effector) functions. To better understand the change of trypsin/CGRP in acute pancreatitis, the study investigated the serum level of trypsin/CGRP in patients with acute pancreatitis...
January 1, 2018: Clinical Laboratory
Daichi Utsumi, Kenjiro Matsumoto, Takuya Tsukahara, Kikuko Amagase, Makoto Tominaga, Shinichi Kato
Transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1), which are non-selective cation channels, play important roles in the sensation of pain. This study investigated the roles of TRPV1 and TRPA1 in dextran sulfate sodium (DSS)-induced murine colitis. DSS (2%) administered for 7 days caused severe colitis that was significantly less severe in TRPV1-deficient (TRPV1KO) and TRPA1-deficient (TRPA1KO) mice than that in wild-type (WT) mice. Similar colitis attenuations were observed in TRPV1KO and TRPA1KO mice but not in WT mice that had been transplanted with bone marrow cells from WT, TRPA1KO, or TRPV1KO mice...
February 8, 2018: Journal of Pharmacological Sciences
Tsugunobu Andoh, Yuta Asakawa, Yasushi Kuraishi
Chronic skin diseases with itch and dry skin show increased peripheral nerve fiber elongation into the epidermis. However, the characteristics of the elongated nerve fibers remain unclear. Therefore, we investigated the characteristics of the elongated nerve fibers using a dry skin mouse model with itch. In this mouse model, prepared via repetitive treatments with an acetone/ether mixture and water, the stratum corneum water content was decreased, whereas spontaneous scratching and epidermal hyperplasia were increased...
February 20, 2018: Neuroscience Letters
Fei Wang, Minji Wang
OBJECTIVE: To observe the effects for vascular dementia (VD) of kidney essence deficiency among acupuncture at five mind points combined with modified kidney qi decoction, simple acupuncture at five mind points and simple modified kidney qi decoction. METHODS: A total of 180 VD patients were randomly assigned into a combination group, an acupuncture group and a herb group, 60 cases in each one. The conventional western medication and rehabilitation training were for all the patients...
February 12, 2018: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
Antoinette MaassenVanDenBrink, Gisela M Terwindt, Arn M J M van den Maagdenberg
Specific prophylactic migraine treatments are urgently needed because of the unmet needs of many migraine patients. Antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have recently shown efficacy in episodic and chronic migraine and will be available soon.
February 22, 2018: Genome Medicine
Jianmin Chen, Alexander J P Hamers, Michaela Finsterbusch, Gianmichele Massimo, Maleeha Zafar, Roger Corder, Romain A Colas, Jesmond Dalli, Christoph Thiemermann, Amrita Ahluwalia
The severity of cardiac dysfunction predicts mortality in sepsis. Activation of transient receptor potential vanilloid receptor type (TRPV)-1, a predominantly neuronal nonselective cation channel, has been shown to improve outcome in sepsis and endotoxemia. However, the role of TRPV1 and the identity of its endogenous ligands in the cardiac dysfunction caused by sepsis and endotoxemia are unknown. Using TRPV1-/- and TRPV1+/+ mice, we showed that endogenous activation of cardiac TRPV1 during sepsis is key to limiting the ensuing cardiac dysfunction...
February 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Min Liu, Huan Chen, Min Tong, Jinping Zhou, Xiyu Wu
STUDY DESIGN: Seventy-five Sprague-Dawley (SD)rats were randomly divided into sham, complete spinal cord transection (CSCT)and hyperbaric oxygen (HBO) groups. Among them, rats in HBO group were further divided into 3 h group (HBO1) and 12 h group (HBO2). OBJECTIVE: To study the effects of ultra-early HBO therapy on femoral calcitonin gene-related peptide (CGRP) and bone metabolism of rats with CSCT. SUMMARY OF BACKGROUND DATA: Complete SCI is still an unresolved problem in clinical practice...
February 16, 2018: Spine
M Dekanosidze, K Saganelidze, N Mitagvaria
It is known that in some pathological conditions, due to the formation of a large number of free oxygen radicals, the cardiovascular system is severely affected. However, the effect of free radicals on CGRP-mediated vasodilation remains unclear. The aim of this work was to study the effect of free radicals on CGRP-mediated neurogenic vasodilation on preparations of an isolated rabbit lingual artery. The experiments were performed on the lingual artery preparations of 6 rabbits of the Chinchilla breed of both sexes...
January 2018: Georgian Medical News
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