Urinary bladder inflammation induces changes in urothelial nerve growth factor and<scp>TRPV</scp>1 channels

Coelho, Ana; Shinde, S.; Cruz, Carlos Oliveira; Cruz, Francisco; Avelino, António; Birder, Lori A.

doi:10.1111/bph.12958

Cited by 36 publications

(36 citation statements)

References 51 publications

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“…Under inflammatory conditions, a TrKA blocker was able to inhibit pain behavior. Furthermore, bladder inflammation increased expression of TRPV1 channels in the membrane of urothelial cells . Mechanical bladder hyperactivity, typical of cystitis, was antagonized by a TRPV1 blocker and was not revealed in TRPV1 KO mice .…”

Section: Pathophysiological Rolesmentioning

confidence: 95%

Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists

Tabrizi

Baraldi

et al. 2016

Medicinal Research Reviews

119

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Transient receptor potential vanilloid 1 (TRPV1) is an ion channel expressed on sensory neurons triggering an influx of cations. TRPV1 receptors function as homotetramers responsive to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Its phosphorylation increases sensitivity to both chemical and thermal stimuli, while desensitization involves a calcium-dependent mechanism resulting in receptor dephosphorylation. TRPV1 functions as a sensor of noxious stimuli and may represent a target to avoid pain and injury. TRPV1 activation has been associated to chronic inflammatory pain and peripheral neuropathy. Its expression is also detected in nonneuronal areas such as bladder, lungs, and cochlea where TRPV1 activation is responsible for pathology development of cystitis, asthma, and hearing loss. This review offers a comprehensive overview about TRPV1 receptor in the pathophysiology of chronic pain, epilepsy, cough, bladder disorders, diabetes, obesity, and hearing loss, highlighting how drug development targeting this channel could have a clinical therapeutic potential. Furthermore, it summarizes the advances of medicinal chemistry research leading to the identification of highly selective TRPV1 antagonists and their analysis of structure-activity relationships (SARs) focusing on new strategies to target this channel.

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Section: Pathophysiological Rolesmentioning

confidence: 95%

Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists

Tabrizi

Baraldi

et al. 2016

Medicinal Research Reviews

119

View full text Add to dashboard Cite

show abstract

“…For instance, colonic NGF and TrkA expression were increased in inflammatory bowel disease (IBD) patients (di Mola et al, 2000), and the NGF level in ulcerative colitis was positively correlated with the severity of the disease . In rat models of chemically-induced cystitis, rats exhibited inflammatory bladder pain, skin mechanical hypersensitivity, and increased NGF content in the bladder mucosa; administration of TrkA antagonist before modeling prevented bladder and skin hyperalgesia, suggesting that coupled with TrkA, NGF transmits signals to the sensory neurons, activates pain pathway, and mediates hypersensitivity (Coelho et al, 2015).…”

Section: Mechanisms Of Ngf-mediated Vhmentioning

confidence: 99%

Nerve growth factor and diarrhea-predominant irritable bowel syndrome (IBS-D): a potential therapeutic target?

Liu

Yao

2016

J. Zhejiang Univ. Sci. B

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Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort associated with abnormal bowel habits. Diarrhea-predominant IBS (IBS-D) is a major subtype of IBS, the predominant manifestations of which are abdominal pain and diarrhea. The pathogenesis of IBS-D remained unknown until recently. The effects of psychosocial stress, central hypervigilance, neuroendocrine abnormality, disturbed gastrointestinal motility, mucosal immune activation, intestinal barrier dysfunction, visceral hypersensitivity (VH), altered gut flora, and genetic susceptibility may be involved in its development. Recently, increased attention has been placed on the neural-immune-endocrine network mechanism in IBS-D, especially the role of various neuroendocrine mediators. As a member of the neurotrophin family, nerve growth factor (NGF) has diverse biological effects, and participates in the pathogenesis of many diseases. Basic studies have demonstrated that NGF is associated with inflammatory-and stress-related VH, as well as stress-related intestinal barrier dysfunction. The aim of this study is to summarize recent literature and discuss the role of NGF in the pathophysiology of IBS-D, especially in VH and intestinal barrier dysfunction, as well as its potential as a therapeutic target in IBS-D.

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“…A study using TRPV1 knockout mice showed that TRPV1 regulated bladder function and mechanically evoked signaling . IL‐1β and NGF promoted the expression of TRPV1 . The bladders of patients with OAB showed chronic inflammation and increased expression of TRPV1 .…”

Section: Discussionmentioning

confidence: 99%

Perilla extract improves frequent urination in spontaneously hypertensive rats with enhancement of the urothelial presence and anti‐inflammatory effects

et al. 2017

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Urinary bladder inflammation induces changes in urothelial nerve growth factor andTRPV1 channels

Abstract: During bladder inflammation, increased production of NGF in urothelial cells induced increased expression and activity of TRPV1 channels in the cell membrane. This effect was primarily mediated by the PI3K pathway.

Cited by 36 publications

References 51 publications

Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists

Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists

Nerve growth factor and diarrhea-predominant irritable bowel syndrome (IBS-D): a potential therapeutic target?

Perilla extract improves frequent urination in spontaneously hypertensive rats with enhancement of the urothelial presence and anti‐inflammatory effects

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