The selective TRPV4 channel antagonist HC-067047 attenuates mechanical allodynia in diabetic mice

Dias, Fabiana C.; Alves, Vinícius Santos; Matias, Daiane O.; Figueiredo, Cláudia P.; Miranda, Ana Luísa P.; Passos, Giselle F.; Costa, Robson

doi:10.1016/j.ejphar.2019.172408

Cited by 36 publications

(27 citation statements)

References 58 publications

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“…Immunohistochemical analysis shows no difference in the level of Trpv4 in the hind paw skin, sciatic nerve, and DRG between diabetic and non‐diabetic mice 48 . As TRPV4 is constitutively expressed and capable of spontaneous activation in the absence of agonist stimulation, Dias et al.…”

Section: Trpv4 and Diabetic Neuropathic Painmentioning

confidence: 99%

“…In type 2 diabetes rodent models, TRPV4 agonists promote vasodilation and improve cardiovascular function 43 . In addition, TRPV4 antagonists reduce HFD‐induced obesity and insulin resistance, and alleviate the progression of diabetic nephropathy, retinopathy and neuropathy 10,12,39,48 .…”

Section: Trpv4 and Diabetes‐related Complicationsmentioning

confidence: 99%

“…Dias et al. 48 showed that HC‐067047, a TRPV4 inhibitor, can hinder the progression of mechanical allodynia in diabetic mice induced by streptozotocin. Similarly, streptozotocin‐induced mechanical hyperalgesia is also weakened in Trpv4 –/– mice 11 .…”

Section: Trpv4 and Diabetic Neuropathic Painmentioning

confidence: 99%

“…Furthermore, inhibiting or attenuating TRPV4 activity might reduce high‐fat diet (HFD)‐induced obesity and inflammation 10 . Table 1 summarizes recent findings on the involvement of TRPV4 in the pathogenesis of type 2 diabetes and diabetes‐related diseases 9‐49 . Even though TRPV4 might play a significant role in the development of diabetes and related conditions, the underlying mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…These compounds include the arachidonic acid metabolite 5,6‐epoxyeicosatrienoic acid (5,6‐EET), acetylcholine, dimethylallyl pyrophosphate, and the endocannabinoid anandamide 59‐62 . In addition, chemicals, such as gadolinium, lanthanum and ruthenium red, botanical extracts, such as bisandrographolide and apigenin 63,64 , and synthetic compounds, including phorbol ester 4α‐phorbol 12,13‐didecanoate (4αPDD), can also affect TRPV4 activity 48,65‐69 . TRPV4 antagonists have been successfully used in vivo for pulmonary edema induced by heart failure, and one of them, GSK2798745, is currently being evaluated in a clinical trial for heart failure 58,70 .…”

Section: Brief Introduction Of Trpv4 Channelmentioning

confidence: 99%

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Transient receptor potential vanilloid 4 channels as therapeutic targets in diabetes and diabetes‐related complications

Ding

et al. 2020

J of Diabetes Invest

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With an estimated 425 million diabetes patients worldwide in 2019, type 2 diabetes has reached a pandemic proportion and represents a major unmet medical need. A key determinant of the development and progression of type 2 diabetes is pancreatic-cell dysfunction, including the loss of cell mass, the impairment of insulin biosynthesis and inadequate exocytosis. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), a Ca 2+-permeable non-selective cation channel, is involved in-cell replication, insulin production and secretion. TRPV4 agonists have insulinotropic activity in pancreatic-cell lines, but the prolonged activation of TRPV4 leads to-cell dysfunction and death. In addition, TRPV4 is involved in a wide variety of pathophysiological activities, and has been reported to play an important role in diabetes-related complications, such as obesity, cardiovascular diseases, diabetic retinopathy, nephropathy and neuropathy. In a rodent type 2 diabetes model, Trpv4 agonists promote vasodilation and improve cardiovascular function, whereas Trpv4 antagonists reduce high-fat diet-induced obesity, insulin resistance, diabetic nephropathy, retinopathy and neuropathy. These findings raise interest in using TRPV4 as a therapeutic target for type 2 diabetes. In this review, we intend to summarize the latest findings regarding the role of TRPV4 in diabetes as well as diabetesrelated conditions, and to evaluate its potential as a therapeutic target for diabetes and diabetes-related diseases.

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Section: Trpv4 and Diabetic Neuropathic Painmentioning

confidence: 99%

Section: Trpv4 and Diabetes‐related Complicationsmentioning

confidence: 99%

Section: Trpv4 and Diabetic Neuropathic Painmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Brief Introduction Of Trpv4 Channelmentioning

confidence: 99%

See 3 more Smart Citations

Transient receptor potential vanilloid 4 channels as therapeutic targets in diabetes and diabetes‐related complications

Ding

et al. 2020

J of Diabetes Invest

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Multidisciplinary Advances Address the Challenges in Developing Drugs against Transient Receptor Potential Channels to Treat Metabolic Disorders

Wang

2023

ChemMedChem

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Transient receptor potential (TRP) channels are cation channels that regulate key physiological and pathological processes in response to a broad range of stimuli. Moreover, they systemically regulate the release of hormones, metabolic homeostasis, and complications of diabetes, which positions them as promising therapeutic targets to combat metabolic disorders. Nevertheless, there are significant challenges in the design of TRP ligands with high potency and durability. Herein we summarize the four challenges as hydrophobicity, selectivity, mono‐target therapy, and interspecies discrepancy. We present 1134 TRP ligands with diversified modes of TRP‐ligand interaction and provide a detailed discussion of the latest strategies, especially cryogenic electron microscopy (cryo‐EM) and computational methods. We propose solutions to address the challenges with a critical analysis of advances in membrane partitioning, polypharmacology, biased agonism, and biochemical screening of transcriptional modulators. They are fueled by the breakthrough from cryo‐EM, chemoinformatics and bioinformatics. The discussion is aimed to shed new light on designing next‐generation drugs to treat obesity, diabetes and its complications, with optimal hydrophobicity, higher mode selectivity, multi‐targeting and consistent activities between human and rodents.

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The Emerging Pro-Algesic Profile of Transient Receptor Potential Vanilloid Type 4

White

Cibelli

Nagy

et al. 2022

Reviews of Physiology, Biochemistry and Pharmacology

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The selective TRPV4 channel antagonist HC-067047 attenuates mechanical allodynia in diabetic mice

Cited by 36 publications

References 58 publications

Transient receptor potential vanilloid 4 channels as therapeutic targets in diabetes and diabetes‐related complications

Transient receptor potential vanilloid 4 channels as therapeutic targets in diabetes and diabetes‐related complications

Multidisciplinary Advances Address the Challenges in Developing Drugs against Transient Receptor Potential Channels to Treat Metabolic Disorders

The Emerging Pro-Algesic Profile of Transient Receptor Potential Vanilloid Type 4

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