Adrian E Morelli, Tina L Sumpter, Darling M Rojas-Canales, Mohna Bandyopadhyay, Zhizhao Chen, Olga Tkacheva, William J Shufesky, Callen T Wallace, Simon C Watkins, Alexandra Berger, Christopher J Paige, Louis D Falo, Adriana T Larregina
Efficient Ca2+ flux induced during cognate T cell activation requires signaling the T cell receptor (TCR) and unidentified G-protein-coupled receptors (GPCRs). T cells express the neurokinin-1 receptor (NK1R), a GPCR that mediates Ca2+ flux in excitable and non-excitable cells. However, the role of the NK1R in TCR signaling remains unknown. We show that the NK1R and its agonists, the neuropeptides substance P and hemokinin-1, co-localize within the immune synapse during cognate activation of T cells. Simultaneous TCR and NK1R stimulation is necessary for efficient Ca2+ flux and Ca2+ -dependent signaling that sustains the survival of activated T cells and helper 1 (Th1) and Th17 bias...
March 10, 2020: Cell Reports
Jennifer Gherardini, Youhei Uchida, Jonathan A Hardman, Jérémy Chéret, Kimberly Mace, Marta Bertolini, Ralf Paus
Besides monocyte (MO)-derived macrophages (MACs), self-renewing tissue-resident macrophages (trMACs) maintain the intracutaneous MAC pool in murine skin. Here, we have asked whether the same phenomenon occurs in human skin using organ-cultured, full-thickness skin detached from blood circulation and bone marrow. Skin stimulation ex vivo with the neuropeptide substance P (SP), mimicking neurogenic skin inflammation, significantly increased the number of CD68+MACs in the papillary dermis without altering intracutaneous MAC proliferation or apoptosis...
2020: PloS One
Jianguo Zhuang, Na Zang, Chunyan Ye, Fadi Xu
The highly pathogenic H5N1 (HK483) viral infection causes a depressed hypercapnic ventilatory response (dHCVR, 20%↓) at 2 days post-infection (dpi) and death at 7 dpi in mice, but the relevant mechanisms are not fully understood. Glomus cells in the carotid body and catecholaminergic neurons in locus coeruleus (LC), neurokinin 1 receptor (NK1R)-expressing neurons in the retrotrapezoid nucleus (RTN), and serotonergic neurons in the raphe are chemosensitive and responsible for HCVR. We asked if the dHCVR became worse over the infection period with viral replication in these cells/neurons...
January 10, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
Magdalena Chottova Dvorakova, Eliska Mistrova, Renate Paddenberg, Wolfgang Kummer, Jana Slavikova
Substance P (SP) is a neuropeptide engaged in the signal transmission of neural C fibers afferents in the myocardium. The actions of SP in the heart are extensive and they are mediated by the neurokinin 1 receptor (NK1R), a member of the tachykinin subfamily of G-protein coupled receptors. The receptors have been found in the heart, but to our knowledge, their exact localization in the heart has not been described yet. Here, we investigated the presence of NK1R protein in separate rat heart compartments by means of western blot and its tissue distribution by means of immunofluorescence...
2018: Frontiers in Physiology
Sergei Spitsin, Vasiliki Pappa, Steven D Douglas
Substance P (SP) is a tachykinin peptide, which triggers intracellular signaling in the nervous and immune systems, as well as, other local and systemic events. The interaction between SP and its receptor, neurokinin-1 receptor (NK1R), results in major downstream cellular actions, which include changes in calcium fluxes, ERK, and p21-activated kinase phosphorylation and NFκB activation. Two naturally occurring variants of the NK1R, the full-length, 407 aa receptor (NK1R-F) and the truncated, 311 aa isoform (NK1R-T), mediate the actions of SP...
January 10, 2018: Journal of Leukocyte Biology
Fiona M Bright, Roger W Byard, Robert Vink, David S Paterson
Substance P (SP) and its tachykinin NK1 receptor (NK1R) function within key medullary nuclei to regulate cardiorespiratory and autonomic control. We examined the normative distribution of SP and NK1R in the serotonergic (5-Hydroxytryptamine, [5-HT]) network of the human infant medulla during postnatal development, to provide a baseline to facilitate future analysis of the SP/NK1R system and its interaction with 5-HT within pediatric brainstem disorders in early life. [125 I] labelled Bolton Hunter SP (BH-SP) tissue receptor autoradiography (n = 15), single label immunohistochemistry (IHC) and double label immunofluorescence (IF) (n = 10) were used to characterize the normative distribution profile of SP and NK1R in the 5-HT network of the human infant medulla during postnatal development...
March 2018: Brain Research Bulletin
Junjun Kang, Weihua Liang, Xiaofeng Huang, Yingying Liu
Objective To explore the changes of cytochrome oxidase (COX) activity in the pre-Botzinger complex (pre-BotC) of the brainstem. Methods The double labeling of COX histochemistry and pre-BotC marker neurokinin-1 receptor (NK1R) nanogold-silver immunohistochemical staining was conducted to determine COX activity in the pre-BotC, especially within different subcellular structures of this nucleus. COX activity was semi-quantitatively analyzed. Results Under the light microscope, NK1R-immunoreactive (NK1R-ir) product was mainly distributed along the neuronal membrane, clearly outlining pre-BotC neurons...
September 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Emily Heath, Billy Chieng, Macdonald J Christie, Bernard W Balleine
It has been recently demonstrated that predictive learning induces a persistent accumulation of delta-opioid receptors (DOPrs) at the somatic membrane of cholinergic interneurons (CINs) in the nucleus accumbens shell (Nac-S). This accumulation is required for predictive learning to influence subsequent choice between goal-directed actions. The current experiments investigated the local neurochemical events responsible for this translocation. We found that (1) local administration of substance P into multiple striatal sub-territories induced DOPr translocation and (2) that this effect was mediated by the NK1 receptor, likely through its expression on CINs...
May 2018: European Journal of Neuroscience
Jianguo Zhuang, Na Zang, Chunyan Ye, Fadi Xu
Lethal influenza A (H5N1) induces respiratory failure in humans. Although it also causes death at 7 days postinfection (dpi) in mice, the development of the respiratory failure and the viral impact on pre-Botzinger complex (PBC) neurons expressing neurokinin 1 receptor (NK1 R), which is the respiratory rhythm generator, have not been explored. Body temperature, weight, ventilation, and arterial blood pH and gases were measured at 0, 2, 4, and 6 dpi in control, lethal HK483, and nonlethal HK486 viral-infected mice...
November 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
Miguel Muñoz, Mario F Muñoz, Antonio Ayala
Substance P (SP) is a neuropeptide belonging to the thachykinin peptide family. SP, after binding to its receptor, the neurokinin 1 receptor (NK1R), controls several transcription factors such as NF-κB, hypoxia inducible factor (HIF-1α), c-myc, c-fos, c-jun, and AP-1. SP and NK1R have a widespread distribution in both the central and peripheral nervous systems. They are also present in cells not belonging to the nervous system (immune cells, placenta, etc.). SP is located in all body fluids, that is, blood, cerebrospinal fluid, etc...
December 2017: Journal of Cellular Biochemistry
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: We sought 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, with the latter reflected in changes in local Toll-like receptor (TLR) expression...
January 2018: 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
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...
January 2017: 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
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