789 HEARTBURN SENSATION IN NON-EROSIVE REFLUX DISEASE: DISTINCTIVE PATTERN OF SUPERFICIAL SENSORY NERVES EXPRESSING TRPV1 AND EPITHELIAL CELLS EXPRESSING ASIC3 RECEPTORS

2021 ◽  
Vol 160 (6) ◽  
pp. S-160-S-161
Author(s):  
Ahsen Ustaoglu ◽  
Chung Lee ◽  
Daniel Sifrim ◽  
Madusha Peiris ◽  
Philip J. Woodland
Keyword(s):  
Epithelial Cells ◽  
Reflux Disease ◽  
Sensory Nerves ◽  
Distinctive Pattern

Heartburn Sensation in Non-Erosive Reflux Disease: Pattern of Superficial Sensory Nerves Expressing TRPV1 and Epithelial Cells Expressing ASIC3 Receptors

2021 ◽  
Author(s):  
Ahsen Ustaoglu ◽  
Akinari Sawada ◽  
Chung Lee ◽  
Wei-Yi Lei ◽  
Chien-Lin Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Reflux Disease ◽  
Transient Receptor Potential ◽  
Sensory Nerve ◽  
Receptor Potential ◽  
Sensory Nerves ◽  
Transient Receptor Potential Vanilloid ◽  
Esophageal Mucosa ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

The underlying causes of heartburn, characteristic symptom of gastro-esophageal reflux disease(GERD), remain incompletely understood. Superficial afferent innervation of the esophageal mucosa in nonerosive reflux disease(NERD) may drive nociceptive reflux perception, but its acid-sensing role has not yet been established. Transient receptor potential vanilloid subfamily member-1(TRPV1), transient receptor potential Melastatin 8(TRPM8), and acid sensing ion channel 3(ASIC3) are regulators of sensory nerve activity and could be important reflux-sensing receptors within the esophageal mucosa. We characterised TRPV1, TRPM8, and ASIC3 expression in esophageal mucosa of GERD patients. We studied 10 NERD, 10 erosive reflux disease(ERD), 7 functional heartburn(FH), and 8 Barrett's esophagus(BE) patients. Biopsies obtained from the distal esophageal mucosa were co-stained with TRPV1, TRPM8, or ASIC3, and CGRP, CD45, or E-cadherin. RNA expression of TRPV1, TRPM8, and ASIC3 was assessed using qPCR. NERD patients had significantly increased expression of TRPV1 on superficial sensory nerves compared to ERD (p=0.028) or BE (p=0.017). Deep intrapapillary nerve endings did not express TRPV1 in all phenotypes studied. ASIC3 was exclusively expressed on epithelial cells most significantly in NERD and ERD patients (p=<0.0001). TRPM8 was expressed on submucosal CD45+ leukocytes. Superficial localisation of TRPV1-immunoreactive nerves in NERD, and increased ASIC3 co-expression on epithelial cells in NERD and ERD suggests a mechanism for heartburn sensation. Esophageal epithelial cells may play a sensory role in acid reflux perception and act interdependently with TRPV1-expressing mucosal nerves to augment hypersensitivity in NERD patients, raising the enticing possibility of topical antagonists for these ion channels as a therapeutic option.

scholarly journals Features of the Expression of Second-Type Melatonin Receptors by Esophagus Epiteliocytes in Gastroesophageal Reflux Disease

2020 ◽  
Vol 30 (2) ◽  
pp. 26-34
Author(s):  
O. A. Karpovich ◽  
T. T. Shtabinskaya ◽  
V. I. Shishko ◽  
Ya. A. Kolodzeysky
Keyword(s):  
Gastroesophageal Reflux Disease ◽  
Epithelial Cells ◽  
Gastroesophageal Reflux ◽  
Mucous Membrane ◽  
Reflux Disease ◽  
Melatonin Receptors ◽  
Control Group ◽  
Expression Intensity ◽  
Low Intensity ◽  
Esophageal Epithelial Cells

Aim. To investigate the specific features of the expression of second-type melatonin receptors (MTNR1B) by epithelial cells of the distal esophagus in gastroesophageal reflux disease (GERD), depending on the severity of endoscopic changes in the mucous membrane.Materials and methods. The study included 48 GERD patients, out of whom 37 and 11 people were suffering from non-erosive reflux disease (NERD) and erosive reflux disease (ERD), respectively. The control group consisted of 18 patients without GERD, comparable with the main groups by gender, age and body mass index. In order to determine the expression of MTNR1B, esophagogastroduodenoscopy with the collection of biopsy material from the mucous membrane of the distal esophagus was performed. The quantification of the MTNR1B expression intensity was carried out using the Aperio ImageScope_v9.1.19.1567 software. The level of melatonin metabolite, 6-sulphatehydroxymelatonin (6-SOMT), was determined in daily urine, as well as separately in daytime and nighttime portions.Results. The intensity of MTNR1B expression by esophageal epithelial cells in patients with NERD demonstrated no difference with the control group (0.436 (0.123, 0.668) and 0.437 (0.202, 0.692), respectively; p> 0.05). A significant decrease in the expression of MTNR1B receptors was noted in patients with ERD compared to NERD patients (0.127 (0.059, 0.156) and 0.436 (0.123, 0.668), respectively; p = 0.017) and patients in the control group (0.437 (0.202, 0.692); p = 0.033). The low intensity of MTNR1B expression was associated with more pronounced endoscopic changes in the mucous membrane of the esophagus (r = –0.40; p = 0.0015). A statistically significant relationship was found between the expression intensity of MTNR1B and the level of melatonin in the daytime (r = 0.42; p = 0.018), as well as the night/day index reflecting the daily rhythm of melatonin synthesis (r = –0.43; p = 0.016).Conclusions. The obtained data indicate that a decrease in the intensity of MTNR1B expression by esophageal epithelial cells can be considered as a prognostically unfavourable sign of the GERD course. The low intensity of MTNR1B expression is associated with a more severe (erosive) form of GERD and more pronounced endoscopic changes in the mucous membrane of the esophagus.

Tachykinin-1 receptor stimulates proinflammatory gene expression in lung epithelial cells through activation of NF-κB via a Gq-dependent pathway

2007 ◽  
Vol 292 (2) ◽  
pp. L430-L437 ◽  
Author(s):  
Ronald Williams ◽  
Xiaoyan Zou ◽  
Gary W. Hoyle
Keyword(s):  
Epithelial Cells ◽  
G Protein ◽  
Intracellular Signaling ◽  
Inflammatory Responses ◽  
Lung Epithelial Cells ◽  
Sensory Nerves ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Intracellular Signaling Pathway ◽  
Lung Epithelial

The respiratory tract is innervated by irritant-responsive sensory nerves, which, on stimulation, release tachykinin neuropeptides in the lung. Tachykinins modulate inflammatory responses to injury by binding to tachykinin (neurokinin) receptors present on various pulmonary cell types. In the present study, the activation of the proinflammatory transcription factor NF-κB in lung epithelial cells was investigated as a mechanism by which tachykinins stimulate inflammatory processes. In A549 human lung epithelial cells transfected with the tachykinin-1 receptor (Tacr1), treatment with the Tacr1 ligand substance P (SP) resulted in NF-κB activation, as judged by transcription of an NF-κB-luciferase reporter gene and production of interleukin-8, a chemokine whose expression is upregulated by NF-κB. SP caused a dose-dependent activation of NF-κB that was inhibited by the selective Tacr1 antagonist RP67580. Tacr1 is a G protein-coupled receptor capable of activating both the Gq and Gs families of G proteins. Expression of inhibitory peptides and constitutively active G protein mutants revealed that Gq signaling was both necessary for Tacr1-induced NF-κB activation and sufficient for NF-κB activation in the absence of any other treatment. Treatment with pharmacological inhibitors to investigate events downstream of Gq revealed that Tacr1-induced NF-κB activation proceeded through an intracellular signaling pathway that was dependent on phospholipase C, calcium, Ras, Raf-1, MEK, Erk, and proteasome function. These results identify intracellular signaling mechanisms that underlie the proinflammatory effects of tachykinins, which previously have been implicated in lung injury and disease.

scholarly journals Corneal epithelial cells function as surrogate Schwann cells for their sensory nerves

Glia ◽  
2016 ◽  
Vol 65 (6) ◽  
pp. 851-863 ◽  
Author(s):  
Mary Ann Stepp ◽  
Gauri Tadvalkar ◽  
Raymond Hakh ◽  
Sonali Pal-Ghosh
Keyword(s):  
Epithelial Cells ◽  
Schwann Cells ◽  
Sensory Nerves ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial

Bombesin stimulates human nasal mucous and serous cell secretion in vivo

1992 ◽  
Vol 262 (1) ◽  
pp. L48-L52 ◽  
Author(s):  
J. N. Baraniuk ◽  
P. B. Silver ◽  
J. D. Lundgren ◽  
P. Cole ◽  
M. A. Kaliner ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Vascular Permeability ◽  
Total Protein ◽  
Mucous Cell ◽  
Sensory Nerves ◽  
Cell Marker ◽  
Cell Secretion ◽  
Submucosal Glands ◽  
Serous Cell

Bombesin, gastrin-related peptide (GRP), and related peptides sharing the common carboxyterminal sequence stimulate lactoferrin (serous cell marker) and glycoconjugate (mucous cell and goblet cell marker) release from human nasal mucosal explants in vitro. In vivo, GRP released from trigeminal sensory nerves may act upon GRP-bombesin binding sites on respiratory epithelial cells and submucosal glands. To determine whether GRP-bombesin can stimulate nasal secretion in vivo, bombesin was administered to eight normal subjects by unilateral, topical administration. Secretions from both nostrils were collected for measurement of total protein, lysozyme, hexose-containing glycoconjugates, and albumin (marker of vascular permeability). Baseline secretions contained 72.0 +/- 17.3 micrograms/ml of total protein, 14 +/- 2 micrograms/ml of lysozyme, 113 +/- 44 micrograms/ml of hexose-containing glycoconjugates, and 7.8 +/- 3.4 micrograms/ml of albumin. Hexose-containing glycoconjugate secretion was significantly increased after 1 nmol (385 +/- 63 micrograms/ml, P less than 0.001 by analysis of variance), 10, 100, and 1,000 nmol of bombesin, but the secretion was not dose dependent. Significant lysozyme (24 +/- 3 micrograms/ml, P less than 0.05) and total protein (155 +/- 23 micrograms/ml, P less than 0.01) secretion occurred after 1,000 nmol. No statistically significant changes in albumin secretion occurred at any dose. Saline had no significant effects on secretion. Therefore, bombesin stimulated secretion from submucosal glands and possibly epithelial cells in the human nose without affecting vascular permeability.

Migration and proliferation of guinea pig and human airway epithelial cells in response to tachykinins

1995 ◽  
Vol 269 (1) ◽  
pp. L119-L126 ◽  
Author(s):  
J. S. Kim ◽  
K. F. Rabe ◽  
H. Magnussen ◽  
J. M. Green ◽  
S. R. White
Keyword(s):  
Epithelial Cells ◽  
Guinea Pig ◽  
Airway Epithelial Cells ◽  
Sensory Nerves ◽  
Neurokinin A ◽  
Airway Epithelial ◽  
Bronchial Epithelial ◽  
Airway Mucosa ◽  
Epithelial Cell Migration ◽  
Tracheal Epithelial

Restoration of the epithelial lining of a damaged airway is a necessary component of airway repair. Tachykinins, including substance P (SP) and neurokinin A (NKA), are localized to sensory nerves within the airway mucosa. These tachykinins regulate several airway functions, but their role in the repair of the epithelium has not been explored. To determine whether tachykinins stimulate migration and proliferation of airway epithelial cells, guinea pig tracheal epithelial (GPTE) and human bronchial epithelial (HBE) cells were grown in primary culture for 4-5 days. Epithelial cell migration was assessed in a blindwell chemotaxis chamber, and proliferation was determined by immunohistochemistry after incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU). Both GPTE and HBE cells migrated after stimulation with 10(-11) M NKA [23.0 +/- 3.6 vs. 5.4 +/- 1.2 cells per 10 high-power fields (hpf), P < 0.001, n = 8 for GPTE cells; 18.4 +/- 2.3 vs. 3.8 +/- 0.5 cells per 10 hpf for control, P < 0.001, n = 4 for HBE cells]. Migration was stimulated within 2 h, was maximal after 6 h, and was attenuated substantially by the neurokinin 2 (NKA)-receptor antagonist SR-48968. NKA-stimulated migration was both chemokinetic and chemotactic, and it could be blocked by inhibition of protein synthesis with cyclohexamide, inhibition of microtubular function with colchicine, or inhibition of actin microfilament elongation with cytochalasin D.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Sex-specific airway hyperreactivity and sex-specific transcriptome remodeling in neonatal piglets challenged with intra-airway acid

2019 ◽  
Vol 316 (1) ◽  
pp. L131-L143 ◽  
Author(s):  
Leah R. Reznikov ◽  
Yan Shin J. Liao ◽  
Tongjun Gu ◽  
Katelyn M. Davis ◽  
Shin Ping Kuan ◽  
...  
Keyword(s):  
Gastroesophageal Reflux Disease ◽  
Gastroesophageal Reflux ◽  
Airway Obstruction ◽  
Reflux Disease ◽  
Neural Circuit ◽  
Smooth Muscle Contraction ◽  
Airway Hyperreactivity ◽  
Sensory Nerves ◽  
Neonatal Piglets ◽  
Airway Acidification

Acute airway acidification is a potent stimulus of sensory nerves and occurs commonly with gastroesophageal reflux disease, cystic fibrosis, and asthma. In infants and adults, airway acidification can acutely precipitate asthma-like symptoms, and treatment-resistant asthma can be associated with gastroesophageal reflux disease. Airway protective behaviors, such as mucus secretion and airway smooth muscle contraction, are often exaggerated in asthma. These behaviors are manifested through activation of neural circuits. In some populations, the neural response to acid might be particularly important. For example, the immune response in infants is relatively immature compared with adults. Infants also have a high frequency of gastroesophageal reflux. Thus, in the current study, we compared the transcriptomes of an airway-nervous system circuit (e.g., tracheal epithelia, nodose ganglia, and brain stem) in neonatal piglets challenged with intra-airway acid. We hypothesized that the identification of parallel changes in the transcriptomes of two neutrally connected tissues might reveal the circuit response, and, hence, molecules important for the manifestation of asthma-like features. Intra-airway acid induced airway hyperreactivity and airway obstruction in male piglets. In contrast, female piglets displayed airway obstruction without airway hyperreactivity. Pairwise comparisons revealed parallel changes in genes directly implicated in airway hyperreactivity ( scn10a) in male acid-challenged piglets, whereas acid-challenged females exhibited parallel changes in genes associated with mild asthma ( stat 1 and isg15). These findings reveal sex-specific responses to acute airway acidification and highlight distinct molecules within a neural circuit that might be critical for the manifestation of asthma-like symptoms in pediatric populations.

Electron Microscopic Study of the Epithelium of the Seminal Vesicle of Aging Rats

1974 ◽  
Vol 32 ◽  
pp. 138-139
Author(s):  
V. F. Allison ◽  
G. C. Fink ◽  
G. W. Cearley
Keyword(s):  
Cell Growth ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Seminal Vesicle ◽  
Seminal Vesicles ◽  
Epithelial Layer ◽  
Epithelial Hyperplasia ◽  
Electron Microscopic ◽  
Aging Rats ◽  
Pseudostratified Epithelium

It is well known that epithelial hyperplasia (benign hypertrophy) is common in the aging prostate of dogs and man. In contrast, little evidence is available for abnormal epithelial cell growth in seminal vesicles of aging animals. Recently, enlarged seminal vesicles were reported in senescent mice, however, that enlargement resulted from increased storage of secretion in the lumen and occurred concomitant to epithelial hypoplasia in that species.The present study is concerned with electron microscopic observations of changes occurring in the pseudostratified epithelium of the seminal vescles of aging rats. Special attention is given to certain non-epithelial cells which have entered the epithelial layer.

The Ultrastructure of Monkey Gingival Epithelium

1967 ◽  
Vol 25 ◽  
pp. 16-17
Author(s):  
C.N. Sun
Keyword(s):  
Epithelial Cells ◽  
Macaca Nemestrina ◽  
Stratum Granulosum ◽  
Solution Ph ◽  
Gingival Epithelial Cells ◽  
Stratum Spinosum ◽  
Cell Layers ◽  
Gingival Epithelium ◽  
The Individual ◽  
Different Thickness

The present study demonstrates the ultrastructure of the gingival epithelium of the pig tail monkey (Macaca nemestrina). Specimens were taken from lingual and facial gingival surfaces and fixed in Dalton's chrome osmium solution (pH 7.6) for 1 hr, dehydrated, and then embedded in Epon 812.Tonofibrils are variable in number and structure according to the different region or location of the gingival epithelial cells, the main orientation of which is parallel to the long axis of the cells. The cytoplasm of the basal epithelial cells contains a great number of tonofilaments and numerous mitochondria. The basement membrane is 300 to 400 A thick. In the cells of stratum spinosum, the tonofibrils are densely packed and increased in number (fig. 1 and 3). They seem to take on a somewhat concentric arrangement around the nucleus. The filaments may occur scattered as thin fibrils in the cytoplasm or they may be arranged in bundles of different thickness. The filaments have a diameter about 50 A. In the stratum granulosum, the cells gradually become flatted, the tonofibrils are usually thin, and the individual tonofilaments are clearly distinguishable (fig. 2). The mitochondria and endoplasmic reticulum are seldom seen in these superficial cell layers.

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