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NK1R localization

Olivia Larsson, Lotta Tengroth, Yuan Xu, Rolf Uddman, Susanna Kumlien Georén, Lars-Olaf Cardell
BACKGROUND: Neuropeptides, such as substance P (SP), have long been seen as mediators of widespread, continuous airway inflammation, a process known as neurogenic inflammation. However, this has been difficult to demonstrate clinically, suggesting an alternative role for these signaling molecules. OBJECTIVES: To examine the role of SP in nasal infection, by assessing the release of SP in response to viral stimulation and characterizing the effects of SP on innate immunity, the latter reflected in changes in local Toll-like receptor (TLR) expression...
February 17, 2017: Journal of Allergy and Clinical Immunology
Tomonori Takazawa, Papiya Choudhury, Chi-Kun Tong, Charles M Conway, Grégory Scherrer, Pamela D Flood, Jun Mukai, Amy B MacDermott
The superficial dorsal horn is the synaptic termination site for many peripheral sensory fibers of the somatosensory system. A wide range of sensory modalities are represented by these fibers, including pain, itch, and temperature. Because the involvement of local inhibition in the dorsal horn, specifically that mediated by the inhibitory amino acids GABA and glycine, is so important in signal processing, we investigated regional inhibitory control of excitatory interneurons under control conditions and peripheral inflammation-induced mechanical allodynia...
March 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jun-Jun Kang, Wei-Hua Liang, Chun-Sing Lam, Xiao-Feng Huang, Shou-Jing Yang, Margaret T T Wong-Riley, Man-Lung Fung, Ying-Ying Liu
The rostral ventrolateral medulla (RVLM) contains cardiovascular-related catecholaminergic neurons and respiratory-related pre-Bötzinger complex (pre-BötC) neurons, which are intermingled and functionally connected for coordinating cardiorespiratory activities. Daily acute intermittent hypoxia (dAIH) is known to elicit respiratory plasticity. However, it is unclear if the catecholaminergic neurons directly synapse onto pre-BötC neurons, and if the local circuitry exhibits plasticity when exposed to dAIH...
May 27, 2016: Experimental Neurology
Zexu Dang, Davide Maselli, Gaia Spinetti, Elena Sangalli, Franco Carnelli, Francesco Rosa, Elena Seganfreddo, Fabio Canal, Anna Furlan, Agostino Paccagnella, Emanuela Paiola, Bruno Lorusso, Claudia Specchia, Mattia Albiero, Roberta Cappellari, Angelo Avogaro, Angela Falco, Federico Quaini, Kepeng Ou, Iker Rodriguez-Arabaolaza, Costanza Emanueli, Maria Sambataro, Gian Paolo Fadini, Paolo Madeddu
AIMS/HYPOTHESIS: Upon tissue injury, peripheral sensory neurons release nociceptive factors (e.g. substance P [SP]), which exert local and systemic actions including the recruitment of bone marrow (BM)-derived haematopoietic stem and progenitor cells (HSPCs) endowed with paracrine pro-angiogenic properties. We herein explore whether diabetic neuropathy interferes with these phenomena. METHODS: We first investigated the presence of sensory neuropathy in the BM of patients with type 2 diabetes by immunohistochemistry and morphometry analyses of nerve size and density and assessment of SP release by ELISA...
November 2015: Diabetologia
L Sosulina, C Strippel, H Romo-Parra, A L Walter, T Kanyshkova, S B Sartori, M D Lange, N Singewald, H-C Pape
Substance P (SP) is implicated in stress regulation and affective and anxiety-related behavior. Particularly high expression has been found in the main output region of the amygdala complex, the central amygdala (CE). Here we investigated the cellular mechanisms of SP in CE in vitro, taking advantage of glutamic acid decarboxylase-green fluorescent protein (GAD67-GFP) knockin mice that yield a reliable labeling of GABAergic neurons, which comprise 95% of the neuronal population in the lateral section of CE (CEl)...
October 2015: Journal of Neurophysiology
Jessica R Barson, Kinning Poon, Hui Tin Ho, Mohammad I Alam, Lilia Sanzalone, Sarah F Leibowitz
The paraventricular nucleus of the thalamus (PVT) appears to participate in drug addiction. Recent evidence in rats shows that ethanol drinking is increased by orexin/hypocretin (OX) afferents from the hypothalamus, acting specifically in the anterior (aPVT) rather than posterior (pPVT) PVT subregion. The present study sought to identify neuropeptides transcribed within the PVT, which themselves might contribute to ethanol drinking and possibly mediate the actions of OX. We discovered that substance P (SP) in the aPVT can stimulate intermittent-access ethanol drinking, similar to OX, and that SP receptor [neurokinin 1 receptor/tachykinin receptor 1 (NK1R)] antagonists in this subregion reduce ethanol drinking...
January 2017: Addiction Biology
Francisco M Pinto, Aixa R Bello, Manuel Gallardo-Castro, Francisco Valladares, Teresa A Almeida, Manuel Tena-Sempere, Luz Candenas
The peptides of the tachykinin family participate in the regulation of reproductive function acting at both central and peripheral levels. Our previous data showed that treatment of rats with a tachykinin NK3R antagonist caused a reduction of litter size. In the present study, we analyzed the expression of tachykinins and tachykinin receptors in the rat uterus during early pregnancy. Uterine samples were obtained from early pregnant rats (Days 1-9 of pregnancy) and from nonpregnant rats during the proestrus stage of the ovarian cycle, and real-time quantitative RT-PCR, immunohistochemistry, and Western blot studies were used to investigate the pattern of expression of tachykinins and tachykinin receptors...
August 2015: Biology of Reproduction
Daniel P Poole, TinaMarie Lieu, Juan Carlos Pelayo, Emily M Eriksson, Nicholas A Veldhuis, Nigel W Bunnett
Activated G protein-coupled receptors traffic to endosomes and are sorted to recycling or degradative pathways. Endosomes are also a site of receptor signaling of sustained and pathophysiologically important processes, including inflammation. However, the mechanisms of endosomal sorting of receptors and the impact of disease on trafficking have not been fully defined. We examined the effects of inflammation on the subcellular distribution and trafficking of the substance P (SP) neurokinin 1 receptor (NK1R) in enteric neurons...
August 15, 2015: American Journal of Physiology. Gastrointestinal and Liver Physiology
Clarissa Muere, Suzanne Neumueller, Samantha Olesiak, Justin Miller, Matthew R Hodges, Lawrence Pan, Hubert V Forster
Substance P (SP) and its receptor, neurokinin-1 (NK1R), have been shown to be excitatory modulators of respiratory frequency and to stabilize breathing regularity. Studies in anesthetized mice suggest that tonic activation of NK1Rs is particularly important when other excitatory inputs to the pre-Bötzinger complex in the ventral respiratory column (VRC) are attenuated. Consistent with these findings, muscarinic receptor blockade in the VRC of intact goats elicits an increase in breathing frequency associated with increases in SP and serotonin concentrations, suggesting an involvement of these substances in neuromodulator compensation...
March 15, 2015: Journal of Applied Physiology
Fabio Bignami, Chiara Giacomini, Anna Lorusso, Andrea Aramini, Paolo Rama, Giulio Ferrari
PURPOSE: To determine whether the inhibition of Substance P (SP) activity can reduce corneal neovascularization (CNV) by means of local administration of high-affinity, competitive, tachykinin 1 receptor (NK1R) antagonists Lanepitant and Befetupitant. METHODS: We performed a safety and efficacy study by using (1) two different C57BL/6 mouse models of CNV: alkali burn and sutures; (2) different concentrations; and (3) different routes of administration: topical or subconjunctival...
October 2014: Investigative Ophthalmology & Visual Science
Tina L Sumpter, Chin H Ho, Anna R Pleet, Olga A Tkacheva, William J Shufesky, Darling M Rojas-Canales, Adrian E Morelli, Adriana T Larregina
BACKGROUND: Efficient development of atopic diseases requires interactions between allergen and adjuvant to initiate and amplify the underlying inflammatory responses. Substance P (SP) and hemokinin-1 (HK-1) are neuropeptides that signal through the neurokinin-1 receptor (NK1R) to promote inflammation. Mast cells initiate the symptoms and tissue effects of atopic disorders, secreting TNF and IL-6 after FcεRI cross-linking by antigen-IgE complexes (FcεRI-activated mast cells [FcεRI-MCs])...
April 2015: Journal of Allergy and Clinical Immunology
Rouhollah Mousavizadeh, Ludvig Backman, Robert G McCormack, Alex Scott
OBJECTIVE: Glucocorticoid injections are used by rheumatologists to treat chronic tendinopathy. Surprisingly, the mechanisms by which corticosteroids induce pain relief in this condition have not been investigated. Previous studies have shown local substance P (SP) levels to be correlated with tendon pain and tissue pathology. The objective of this study was to determine whether SP production in human tenocytes is modulated by exposure to dexamethasone. METHODS: Human tendon fibroblasts were cultured in the presence or absence of dexamethasone (1-400 nM), an inhibitor of the glucocorticoid receptor, RU486, recombinant TGF-β (2...
February 2015: Rheumatology
Chi-Kun Tong, Amy B MacDermott
NMDA receptors are important elements in pain signaling in the spinal cord dorsal horn. They are heterotetramers, typically composed of two GluN1 and two of four GluN2 subunits: GluN2A-2D. Mice lacking some of the GluN2 subunits show deficits in pain transmission yet functional synaptic localization of these receptor subtypes in the dorsal horn has not been fully resolved. In this study, we have investigated the composition of synaptic NMDA receptors expressed in monosynaptic and polysynaptic pathways from peripheral sensory fibers to lamina I neurons in rats...
August 13, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Marta V Hamity, Roxanne Y Walder, Donna L Hammond
This study examined possible mechanisms by which Substance P (Sub P) assumes a pronociceptive role in the rostral ventromedial medulla (RVM) under conditions of peripheral inflammatory injury, in this case produced by intraplantar (ipl) injection of complete Freund's adjuvant (CFA). In saline- and CFA-treated rats, neurokinin-1 receptor (NK1R) immunoreactivity was localized to neurons in the RVM. Four days after ipl injection of CFA, the number of NK1R-immunoreactive neurons in the RVM was increased by 30%, and there was a concomitant increase in NK1R-immunoreactive processes in CFA-treated rats...
September 1, 2014: Journal of Comparative Neurology
Toshiharu Azma, Florin Tuluc, Taishin Ito, Chikako Aoyama-Mani, Shinji Kawahito, Hiroyuki Kinoshita
Thrombotic events occurring in either arteries or veins are the primary causes of fatal perioperative cardiovascular events. Risk factors for deep vein thrombosis, several of which are evidently associated with specific surgical procedures, are quite different from those for arterial thrombosis (e.g., aging or atherosclerotic diseases). Thrombus formed in arteries consists mainly of platelets coated with fibrin (i.e., white thrombus), while venous thrombus formed at relatively lower shear stress consists of all blood components including erythrocytes as well as leukocytes infiltrated with fibrin (red thrombus)...
2014: Current Pharmaceutical Design
B K Taylor, W Fu, K E Kuphal, C-O Stiller, M K Winter, W Chen, G F Corder, J H Urban, K E McCarson, J C Marvizon
Neuropeptide Y (NPY) is present in the superficial laminae of the dorsal horn and inhibits spinal nociceptive processing, but the mechanisms underlying its anti-hyperalgesic actions are unclear. We hypothesized that NPY acts at neuropeptide Y1 receptors in the dorsal horn to decrease nociception by inhibiting substance P (SP) release, and that these effects are enhanced by inflammation. To evaluate SP release, we used microdialysis and neurokinin 1 receptor (NK1R) internalization in rat. NPY decreased capsaicin-evoked SP-like immunoreactivity in the microdialysate of the dorsal horn...
January 3, 2014: Neuroscience
Obulakshmi Arapulisamy, Padmanabhan Mannangatti, Lankupalle D Jayanthi
Neurokinin-1 receptor (NK1R) mediates down-regulation of human norepinephrine (NE) transporter (hNET) via protein kinase C (PKC). However, native NET regulation by NK1R and the mechanism by which NK1R targets NET among other potential effectors are unknown. Effect of NK1R activation on native NET regulation and NET/NK1R interaction were studied using rat brain synaptosomes expressing native NET and NK1R as well as human placental trophoblast (HTR) cells coexpressing WT-hNET or NK1R/PKC-resistant hNET-T258A,S259A double mutant (NET-DM) and hNK1R...
October 4, 2013: Journal of Biological Chemistry
Norimasa Yoshida, Masaaki Kuroda, Takahiro Suzuki, Kazuhiro Kamada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Toshikazu Yoshikawa, Hirofumi Kuramoto
BACKGROUND AND AIMS: Esophageal visceral hypersensitivity has been proposed to be a pathogenesis of heartburn in nonerosive reflux disease (NERD), but its further mechanisms are unclear. Recently, it has been suggested that nociceptors and neuropeptides control sensory and pain mechanisms. Therefore, the objective of the present study was to estimate expression of acid-sensitive nociceptors such as transient receptor potential vanilloid 1 (TRPV1) and acid-sensing ion channel 3, protease-activated receptor 2 (PAR2), neuropeptides such as substance P and calcitonin-gene-related peptide, and their receptors such as neurokinin 1 receptor (NK1R) and receptor activity-modifying protein 1 in the esophageal mucosa of NERD patients...
August 2013: Digestive Diseases and Sciences
Nicola Cavallini, Dick Delbro, Gunnar Tobin, Magnus Braide
BACKGROUND: The triggers of the acute local inflammatory response to peritoneal dialysis (PD) fluid exposure remain unknown. In the present study, we investigated the effects of neurogenic inflammation and mast cell degranulation on water and solute transport in experimental PD. METHODS: Single 2-hour dwells in rats with PD catheters were studied. Histamine and the neuropeptides substance P and calcitonin gene-related peptide (CGRP) were measured in PD fluid samples by ELISA...
March 2012: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
Veronica Sánchez Freire, Fiona C Burkhard, Andrea Schmitz, Thomas M Kessler, Katia Monastyrskaya
OBJECTIVE: To establish the mRNA expression profiles of selected genes involved in bladder contractility and epithelial permeability in the bladder dome and trigone in order to evaluate the use of cold-cut biopsies for comparative quantitative studies into the anatomical differences between these two bladder regions. PATIENTS AND METHODS: After informed consent, cold-cut biopsies from the bladder dome and trigone were obtained from eight asymptomatic subjects. RNA was extracted from muscle biopsies, and the expression levels of selected genes were analysed using TaqMan real-time PCR-based gene expression assays...
July 2011: BJU International
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