scholarly journals Blocking PAR2 alleviates bladder pain and hyperactivity via TRPA1 signal

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Daihui Chen ◽  
Nian Liu ◽  
Mao Li ◽  
Simin Liang
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Bladder Pain ◽  
Transient Receptor Potential A1 ◽  
Sensory Activity ◽  
Bladder Activity ◽  
Bladder Disorders ◽  
Transient Receptor ◽  
Underlying Mechanisms

AbstractBladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The goals of this study were to examine 1) the effects of blocking proteinase-activated receptor-2 (PAR2) on the exaggerated bladder activity and pain evoked by cystitis and 2) the underlying mechanisms responsible for the role of PAR2 in regulating cystic sensory activity. The protein expression of PAR2 was amplified in rats with cystitis by inducing it with systemic administration of cyclophosphamide (CYP) as compared with control rats. Blocking PAR2 by intrathecal infusion of PAR2 antagonist FSLLRY-NH2 attenuated bladder hyperactivity and pain. In addition, blocking PAR2 attenuated the transient receptor potential A1 (TRPA1) signal pathway, whereas inhibition of the TRPA1 decreased bladder hyperactivity and pain. The data revealed specific signaling pathways leading to CYP-induced bladder hyperactivity and pain, including the activation of PAR2 and TRPA1. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis.

scholarly journals Role of Transient Receptor Potential A1 in Gastric Nociception

Digestion ◽  
2010 ◽  
Vol 82 (3) ◽  
pp. 150-155 ◽  
Author(s):  
Takashi Kondo ◽  
Tadayuki Oshima ◽  
Koichi Obata ◽  
Jun Sakurai ◽  
Charles H. Knowles ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential A1 ◽  
Transient Receptor

scholarly journals The Role of Transient Receptor Potential A1 and G Protein-Coupled Receptor 39 in Zinc-Mediated Acute and Chronic Itch in Mice

2022 ◽  
Vol 14 ◽  
Author(s):  
Yue Hu ◽  
Qing-Yue Fu ◽  
Dan-Ni Fu ◽  
Xue-Long Wang ◽  
Zhi-Hong Wang ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Systemic Administration ◽  
Common Symptom ◽  
Dry Skin ◽  
C Fibers ◽  
Transient Receptor Potential A1 ◽  
Chronic Itch ◽  
Transient Receptor

Itching is a common symptom of many skin or systemic diseases and has a negative impact on the quality of life. Zinc, one of the most important trace elements in an organism, plays an important role in the regulation of pain. Whether and how zinc regulates itching is largely unclear. Herein, we explored the role of Zn2+ in the regulation of acute and chronic itch in mice. It is found that intradermal injection (i.d.) of Zn2+ dose-dependently induced acute itch and transient receptor potential A1 (TRPA1) participated in Zn2+-induced acute itch in mice. Moreover, the pharmacological analysis showed the involvement of histamine, mast cells, opioid receptors, and capsaicin-sensitive C-fibers in Zn2+-induced acute itch in mice. Systemic administration of Zn2+ chelators, such as N,N,N′,N′-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), pyrithione, and clioquinol were able to attenuate both acute itch and dry skin-induced chronic itch in mice. Quantitative polymerase chain reaction (Q-PCR) analysis showed that the messenger RNA (mRNA) expression levels of zinc transporters (ZIPs and ZnTs) significantly changed in the dorsal root ganglia (DRG) under dry skin-induced chronic itch condition in mice. Activation of extracellular signal-regulated kinase (ERK) pathway was induced in the DRG and skin by the administration of zinc or under dry skin condition, which was inhibited by systemic administration of Zn2+ chelators. Finally, we found that the expression of GPR39 (a zinc-sensing GPCR) was significantly upregulated in the dry skin mice model and involved in the pathogenesis of chronic itch. Together, these results indicated that the TRPA1/GPR39/ERK axis mediated the zinc-induced itch and, thus, targeting zinc signaling may be a promising strategy for anti-itch therapy.

scholarly journals Role of PAR2 in regulating oxaliplatin-induced neuropathic pain via TRPA1

2015 ◽  
Vol 6 (1) ◽  
pp. 111-116 ◽  
Author(s):  
Liujun Tian ◽  
Tianren Fan ◽  
Nan Zhou ◽  
Hui Guo ◽  
Weijie Zhang
Keyword(s):  
Neuropathic Pain ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cold Sensitivity ◽  
Downstream Signaling ◽  
Lumbar Dorsal Root Ganglion ◽  
Transient Receptor ◽  
Underlying Mechanisms ◽  
Cold Hypersensitivity

AbstractOxaliplatin (OXL) is a third-generation chemotherapeutic agent commonly used to treat metastatic digestive tumors; however, one of the main limiting complications of OXL is neuropathic pain. In this study, the underlying mechanisms responsible for OXL evoked-neuropathic pain were examined. Using a rat model, the results demonstrated that intraperitoneal (i.p.) injection of OXL significantly increased mechanical pain and cold sensitivity as compared with control animals (P < 0.05 vs. control rats). Blocking proteinase-activated receptor 2 (PAR2) significantly attenuated mechanical pain and cold sensitivity observed in control rats and OXL rats (P < 0.05 vs. vehicle control). The attenuating effect of PAR2 on mechanical pain and cold sensitivity were significantly smaller in OXL-rats than in control rats. The role played by PAR2 downstream signaling pathways [namely, transient receptor potential ankyrin 1 (TRPA1)] in regulating OXL evoked-neuropathic pain was also examined. The data shows that TRPA1 expression was upregulated in the lumbar dorsal root ganglion (DRG) of OXL rats and blocking TRPA1 inhibited mechanical pain and heightened cold sensitivity (P <0.05 vs. control rats). Blocking PAR2 also significantly decreased TRPA1expression in the DRG. Findings in this study show that OXL intervention amplifies mechanical hyperalgesia and cold hypersensitivity and PAR2 plays an important role in regulating OXLinduced neuropathic pain via TRPA1 pathways.

scholarly journals Light-regulated interaction of Dmoesin with TRP and TRPL channels is required for maintenance of photoreceptors

2005 ◽  
Vol 171 (1) ◽  
pp. 143-152 ◽  
Author(s):  
Irit Chorna-Ornan ◽  
Vered Tzarfaty ◽  
Galit Ankri-Eliahoo ◽  
Tamar Joel-Almagor ◽  
Nina E. Meyer ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Photoreceptor Cells ◽  
Mutant Form ◽  
Dependent Manner ◽  
Erm Proteins ◽  
Absorption Of Light ◽  
Transient Receptor ◽  
Underlying Mechanisms

Recent studies in Drosophila melanogaster retina indicate that absorption of light causes the translocation of signaling molecules and actin from the photoreceptor's signaling membrane to the cytosol, but the underlying mechanisms are not fully understood. As ezrin-radixin-moesin (ERM) proteins are known to regulate actin–membrane interactions in a signal-dependent manner, we analyzed the role of Dmoesin, the unique D. melanogaster ERM, in response to light. We report that the illumination of dark-raised flies triggers the dissociation of Dmoesin from the light-sensitive transient receptor potential (TRP) and TRP-like channels, followed by the migration of Dmoesin from the membrane to the cytoplasm. Furthermore, we show that light-activated migration of Dmoesin results from the dephosphorylation of a conserved threonine in Dmoesin. The expression of a Dmoesin mutant form that impairs this phosphorylation inhibits Dmoesin movement and leads to light-induced retinal degeneration. Thus, our data strongly suggest that the light- and phosphorylation-dependent dynamic association of Dmoesin to membrane channels is involved in maintenance of the photoreceptor cells.

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