scholarly journals Transient Receptor Potential Vanilloid Subtype 1: Potential Role in Infection, Susceptibility, Symptoms and Treatment of COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Filippo Liviero ◽  
Manuela Campisi ◽  
Paola Mason ◽  
Sofia Pavanello
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Sensory Nerves ◽  
Therapeutic Interventions ◽  
Transient Receptor Potential Vanilloid ◽  
Binding Motifs ◽  
Infection Susceptibility ◽  
Beneficial Action ◽  
Control Infection ◽  
Transient Receptor

The battle against the new coronavirus that continues to kill millions of people will be still long. Novel strategies are demanded to control infection, mitigate symptoms and treatment of COVID-19. This is even more imperative given the long sequels that the disease has on the health of the infected. The discovery that S protein includes two ankyrin binding motifs (S-ARBMs) and that the transient receptor potential vanilloid subtype 1 (TRPV-1) cation channels contain these ankyrin repeat domains (TRPs-ARDs) suggest that TRPV-1, the most studied member of the TRPV channel family, can play a role in binding SARS-CoV-2. This hypothesis is strengthened by studies showing that other respiratory viruses bind the TRPV-1 on sensory nerves and epithelial cells in the airways. Furthermore, the pathophysiology in COVID-19 patients is similar to the effects generated by TRPV-1 stimulation. Lastly, treatment with agonists that down-regulate or inactivate TRPV-1 can have a beneficial action on impaired lung functions and clearance of infection. In this review, we explore the role of the TRPV-1 channel in the infection, susceptibility, pathogenesis, and treatment of COVID-19, with the aim of looking at novel strategies to control infection and mitigate symptoms, and trying to translate this knowledge into new preventive and therapeutic interventions.

scholarly journals NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases

2022 ◽  
Vol 23 (2) ◽  
pp. 892
Author(s):  
Mariia Belinskaia ◽  
Tomas Zurawski ◽  
Seshu Kumar Kaza ◽  
Caren Antoniazzi ◽  
J. Oliver Dolly ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Sensory Nerves ◽  
Neonatal Rat ◽  
Transient Receptor Potential Vanilloid ◽  
C Terminus ◽  
Low Concentrations ◽  
Transient Receptor ◽  
Neuronal Functions ◽  
Differential Ability

Nerve growth factor (NGF) is known to intensify pain in various ways, so perturbing pertinent effects without negating its essential influences on neuronal functions could help the search for much-needed analgesics. Towards this goal, cultured neurons from neonatal rat trigeminal ganglia—a locus for craniofacial sensory nerves—were used to examine how NGF affects the Ca2+-dependent release of a pain mediator, calcitonin gene-related peptide (CGRP), that is triggered by activating a key signal transducer, transient receptor potential vanilloid 1 (TRPV1) with capsaicin (CAP). Measurements utilised neurons fed with or deprived of NGF for 2 days. Acute re-introduction of NGF induced Ca2+-dependent CGRP exocytosis that was inhibited by botulinum neurotoxin type A (BoNT/A) or a chimera of/E and/A (/EA), which truncated SNAP-25 (synaptosomal-associated protein with Mr = 25 k) at distinct sites. NGF additionally caused a Ca2+-independent enhancement of the neuropeptide release evoked by low concentrations (<100 nM) of CAP, but only marginally increased the peak response to ≥100 nM. Notably, BoNT/A inhibited CGRP exocytosis evoked by low but not high CAP concentrations, whereas/EA effectively reduced responses up to 1 µM CAP and inhibited to a greater extent its enhancement by NGF. In addition to establishing that sensitisation of sensory neurons to CAP by NGF is dependent on SNARE-mediated membrane fusion, insights were gleaned into the differential ability of two regions in the C-terminus of SNAP-25 (181–197 and 198–206) to support CAP-evoked Ca2+-dependent exocytosis at different intensities of stimulation.

scholarly journals Sex-dependent expression of TRPV1 in bladder arterioles

2016 ◽  
Vol 311 (5) ◽  
pp. F1063-F1073 ◽  
Author(s):  
Thieu X. Phan ◽  
Hoai T. Ton ◽  
Yue Chen ◽  
Maureen E. Basha ◽  
Gerard P. Ahern
Keyword(s):  
Transient Receptor Potential ◽  
Small Diameter ◽  
Receptor Potential ◽  
Sensory Nerves ◽  
Transient Receptor Potential Vanilloid ◽  
Equal Distribution ◽  
Bladder Dome ◽  
Inflammatory Conditions ◽  
Trpv1 Channels ◽  
Transient Receptor

Transient receptor potential vanilloid type 1 (TRPV1) is a major nociceptive ion channel implicated in bladder physiology and/or pathophysiology. However, the precise expression of TRPV1 in neuronal vs. nonneuronal bladder cells is uncertain. Here we used reporter mouse lines (TRPV1-Cre:tdTomato and TRPV1PLAP-nlacZ) to map expression of TRPV1 in postnatal bladder. TRPV1 was not detected in the urothelium, however, we found marked expression of TRPV1 lineage in sensory nerves, and surprisingly, in arterial/arteriolar smooth muscle (ASM) cells. Tomato fluorescence was prominent in the vesical arteries and in small-diameter (15–40 μm) arterioles located in the suburothelial layer with a near equal distribution in bladder dome and base. Notably, arteriolar TRPV1 expression was greater in females than in males and increased in both sexes after 90 days of age, suggesting sex hormone and age dependency. Analysis of whole bladder and vesical artery TRPV1 mRNA revealed a similar sex and developmental dependence. Pharmacological experiments confirmed functional TRPV1 protein expression; capsaicin increased intracellular Ca2+ in ∼15% of ASM cells from wild-type female bladders, but we observed no responses to capsaicin in bladder arterioles isolated from TRPV1-null mice. Furthermore, capsaicin triggered arteriole constriction that was rapidly reversed by the TRPV1 antagonist, BCTC. These data show that predominantly in postpubertal female mice, bladder ASM cells express functional TRPV1 channels that may act to constrict arterioles. TRPV1 may therefore play an important role in regulating the microcirculation of the female bladder, and this effect may be of significance during inflammatory conditions.

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 TRPV1-mediated protection against endotoxin-induced hypotension and mortality in rats

2008 ◽  
Vol 294 (5) ◽  
pp. R1517-R1523 ◽  
Author(s):  
Youping Wang ◽  
Martin Novotný ◽  
Veronika Quaiserová-Mocko ◽  
Greg M. Swain ◽  
Donna H. Wang
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Protective Role ◽  
Sensory Nerves ◽  
Transient Receptor Potential Vanilloid ◽  
Induced Hypotension ◽  
Trpv1 Receptors ◽  
Male Wistar Rats ◽  
Neurokinin 1 ◽  
Transient Receptor

This study was designed to test the hypothesis that the transient receptor potential vanilloid type 1 (TRPV1) channel, expressed primarily in sensory nerves, and substance P (SP), released by sensory nerves, play a protective role against lipopolysaccharide (LPS)-induced hypotension. LPS (10 mg/kg iv) elicited tachycardia and hypotension in anesthetized male Wistar rats, which peaked at 10 min and gradually recovered 1 h after the injection. Blockade of TRPV1 with its selective antagonist capsazepine (CAPZ, 3 mg/kg iv) impaired recovery given that the fall in mean arterial pressure (MAP) was greater 1 h after CAPZ plus LPS injections compared with LPS injection alone (45 ± 5 vs. 25 ± 4 mmHg, P < 0.05). Blockade of the neurokinin 1 (NK1) receptor with its selective antagonists RP-67580 (5 mg/kg iv) or L-733,060 (4 mg/kg iv) prevented recovery, considering that falls in MAP were not different 1 h after injections of NK1 antagonists plus LPS from their peak decreases (66 ± 9 vs. 74 ± 5 mmHg or 60 ± 7 vs. 69 ± 3 mmHg, respectively, P > 0.05). LPS increased plasma SP, norepinephrine (NE), and epinephrine (Epi) levels compared with vehicles, and the increases in plasma SP, NE, and Epi were significantly inhibited by CAPZ or RP-67580. The survival rate at 24 or 48 h after LPS injection (20 mg/kg ip) was lower in conscious rats pretreated with CAPZ or RP-67580 compared with rats treated with LPS alone ( P < 0.05). Thus our results show that the TRPV1, possibly via triggering release of SP which activates the NK1 and stimulates the sympathetic axis, plays a protective role against endotoxin-induced hypotension and mortality, suggesting that TRPV1 receptors are essential in protecting vital organ perfusion and survival during the endotoxic condition.

Transient receptor potential vanilloid 1, calcitonin gene-related peptide, and substance P mediate nociception in acute pancreatitis

2006 ◽  
Vol 290 (5) ◽  
pp. G959-G969 ◽  
Author(s):  
Elizabeth C. Wick ◽  
Steven G. Hoge ◽  
Sarah W. Grahn ◽  
Edward Kim ◽  
Lorna A. Divino ◽  
...  
Keyword(s):  
Substance P ◽  
Dorsal Horn ◽  
Transient Receptor Potential ◽  
Necrotizing Pancreatitis ◽  
Receptor Potential ◽  
Sensory Nerves ◽  
Transient Receptor Potential Vanilloid ◽  
Spinal Neurons ◽  
Fos Expression ◽  
Transient Receptor

The mechanism of pancreatitis-induced pain is unknown. In other tissues, inflammation activates transient receptor potential vanilloid 1 (TRPV1) on sensory nerves to liberate CGRP and substance P (SP) in peripheral tissues and the dorsal horn to cause neurogenic inflammation and pain, respectively. We evaluated the contribution of TRPV1, CGRP, and SP to pancreatic pain in rats. TRPV1, CGRP, and SP were coexpressed in nerve fibers of the pancreas. Injection of the TRPV1 agonist capsaicin into the pancreatic duct induced endocytosis of the neurokinin 1 receptor in spinal neurons in the dorsal horn (T10), indicative of SP release upon stimulation of pancreatic sensory nerves. Induction of necrotizing pancreatitis by treatment with l-arginine caused a 12-fold increase in the number of spinal neurons expressing the proto-oncogene c-fos in laminae I and II of L1, suggesting activation of nociceptive pathways. l-Arginine also caused a threefold increase in spontaneous abdominal contractions detected by electromyography, suggestive of referred pain. Systemic administration of the TRPV1 antagonist capsazepine inhibited c-fos expression by 2.5-fold and abdominal contractions by 4-fold. Intrathecal, but not systemic, administration of antagonists of CGRP (CGRP8–37) and SP (SR140333) receptors attenuated c-fos expression in spinal neurons by twofold. Thus necrotizing pancreatitis activates TRPV1 on pancreatic sensory nerves to release SP and CGRP in the dorsal horn, resulting in nociception. Antagonism of TRPV1, SP, and CGRP receptors may suppress pancreatitis pain.

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