scholarly journals TRPV4 activation in mouse submandibular gland modulates Ca2+ influx and salivation

2012 ◽  
Vol 303 (12) ◽  
pp. G1365-G1372 ◽  
Author(s):  
Yan Zhang ◽  
Marcelo A. Catalán ◽  
James E. Melvin
Keyword(s):  
Submandibular Gland ◽  
Transient Receptor Potential ◽  
Basolateral Membrane ◽  
Acinar Cells ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Secretion Pathway ◽  
Acid Metabolites ◽  
Transient Receptor ◽  
And Function

Transient receptor potential vanilloid subtype 4 (TRPV4) is a ligand-gated nonselective cation channel that participates in the transduction of mechanical and osmotic stimuli in different tissues. TRPV4 is activated by endogenous arachidonic acid metabolites, 4α-phorbol-12,13 didecanoate, GSK1016790A, moderate heat, and mechanical stress. TRPV4 is expressed in the salivary glands, but its expression pattern and function are poorly understood. The aim of this study was to evaluate the functional role of TRPV4 channels in the mouse submandibular gland. Using RT-PCR and Western blot analysis, we detected expression of TRPV4 message and protein, respectively, in the submandibular gland. Immunolocalization studies showed that TRPV4 targeted to the basolateral membrane of mouse submandibular gland acinar cells. Pharmacological TRPV4 activation using the selective agonist GSK1016790A caused Ca2+ influx in isolated acinar cells in a basal-to-apical wave. Consistent with these observations, GSK1016790A elicited salivation in the perfused submandibular gland that was dependent on extracellular Ca2+. In summary, we report that activation of TRPV4 channels induced Ca2+ influx and salivation and, thus, may contribute a novel nonadrenergic, noncholinergic secretion pathway in the mouse submandibular gland.

scholarly journals Leukemia cells remodel marrow adipocytes via TRPV4-dependent lipolysis

Haematologica ◽  
2019 ◽  
Vol 105 (11) ◽  
pp. 2572-2583
Author(s):  
Shaoxin Yang ◽  
Wei Lu ◽  
Chong Zhao ◽  
Yuanmei Zhai ◽  
Yanyu Wei ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Receptor Potential ◽  
Transforming Growth Factor Β ◽  
Leukemia Cells ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor ◽  
Novel Strategy ◽  
And Function

Remodeling of adipocyte morphology and function plays a critical role in prostate cancer development. We previously reported that leukemia cells secrete growth differentiation factor 15 (GDF15)，which remodels the residual bone marrow (BM) adipocytes into small adipocytes and is associated with a poor prognosis in acute myeloid leukemia (AML) patients. However, little is known about how GDF15 drives BM adipocyte remodeling. In this study, we examined the role of the transient receptor potential vanilloid (TRPV) channels in the remodeling of BM adipocytes exposed to GDF15. We found that TRPV4 negatively regulated GDF15-induced remodeling of BM adipocytes. Furthermore, transforming growth factor-β type II receptor (TGFβRII) was identified as the main receptor for GDF15 on BM adipocytes. PI3K inhibitor treatment reduced GDF15-induced pAKT, identifying PI3K/AKT as the downstream stress response pathway. Subsequently, GDF15 reduced the expression of the transcription factor Forkhead box C1 (FOXC1) in BM adipocytes subjected to RNA-seq screening and Western blot analyse. Moreover, it was also confirmed that FOXC1 combined with the TRPV4 promoter by the Chip-qPCR experiments, which suggests that FOXC1 mediates GDF15 regulation of TRPV4. In addition, an AML mouse model exhibited smaller BM adipocytes, whereas the TRPV4 activator 4α-phorbol 12,13-didecanoate (4αPDD) partly rescued this process and increased survival. In conclusion, TRPV4 plays a critical role in BM adipocyte remodeling induced by leukemia cells, suggesting that targeting TRPV4 may constitute a novel strategy for AML therapy.

scholarly journals TRPV4: Molecular Conductor of a Diverse Orchestra

2016 ◽  
Vol 96 (3) ◽  
pp. 911-973 ◽  
Author(s):  
John P. M. White ◽  
Mario Cibelli ◽  
Laszlo Urban ◽  
Bernd Nilius ◽  
J. Graham McGeown ◽  
...  
Keyword(s):  
Ion Channel ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
The Body ◽  
Transient Receptor Potential Vanilloid ◽  
Ionotropic Receptor ◽  
Disease States ◽  
Health And Disease ◽  
Transient Receptor ◽  
And Function

Transient receptor potential vanilloid type 4 (TRPV4) is a calcium-permeable nonselective cation channel, originally described in 2000 by research teams led by Schultz ( Nat Cell Biol 2: 695 –702, 2000) and Liedtke ( Cell 103: 525–535, 2000). TRPV4 is now recognized as being a polymodal ionotropic receptor that is activated by a disparate array of stimuli, ranging from hypotonicity to heat and acidic pH. Importantly, this ion channel is constitutively expressed and capable of spontaneous activity in the absence of agonist stimulation, which suggests that it serves important physiological functions, as does its widespread dissemination throughout the body and its capacity to interact with other proteins. Not surprisingly, therefore, it has emerged more recently that TRPV4 fulfills a great number of important physiological roles and that various disease states are attributable to the absence, or abnormal functioning, of this ion channel. Here, we review the known characteristics of this ion channel's structure, localization and function, including its activators, and examine its functional importance in health and disease.

scholarly journals Spatiotemporal and functional characterisation of transient receptor potential vanilloid 4 (TRPV4) in the murine intervertebral disc

2021 ◽  
Vol 41 ◽  
pp. 194-203
Author(s):  
MKM Kim ◽  
◽  
R Ramachandran ◽  
CA Séguin
Keyword(s):  
Intervertebral Disc ◽  
Transient Receptor Potential ◽  
Skeletal Maturity ◽  
Receptor Potential ◽  
Calcium Oscillation ◽  
Transient Receptor Potential Vanilloid ◽  
Cartilage Endplate ◽  
Functional Characterisation ◽  
Transient Receptor ◽  
And Function

The molecular regulators of mechano-transduction in intervertebral disc (IVD) cells are not well understood. The aim of the present study was to characterise the expression and function of the mechano-sensitive ion channel TRPV4 in the IVD. A novel transgenic reporter mouse, in which the endogenous Trpv4 locus drove the expression of LacZ, was used to localise Trpv4 expression at specific stages of spine development [embryonic day (E) 8.5, 12.5, 17.5, postnatal day 1] and time points following skeletal maturity (2.5, 6, 9 and 12 months). The TRPV4-specific agonist GSK1016790A and antagonist GSK2193874 were used to assess the functional response of annulus fibrosus (AF) cells using epifluorescence imaging with Ca2+-sensitive Fura-2 dye and F-actin staining. The effects of TRPV4 agonism and antagonism in mechanically stimulated AF cells were quantified by gene expression analysis. Trpv4 expression was specific to the developing notochord and intervertebral mesenchyme at E12.5. At 2.5, 6 and 9 months, Trpv4 expression was detected in the nucleus pulposus, inner AF, cartilage endplate and vertebral growth plate. AF cells treated with GSK1016790A demonstrated heterogeneity in TRPV4-dependent Ca2+ responses (no response, calcium oscillation or sustained response). TRPV4-induced Ca2+ signalling was associated with Rho/ROCK-dependent actin cytoskeleton remodelling and stress-fibre formation. In AF cells, cyclic-tensile-strain-induced changes in Acan and Prg4 expression were mediated by TRPV4 channel activation. These data establish TRPV4 as an important mechano- sensor regulating IVD mechano-biology.

scholarly journals Update on the Role of Spinal Cord TRPV1 Receptors in Pain Modulation

2014 ◽  
pp. S225-S236 ◽  
Author(s):  
D. SPICAROVA ◽  
V. NERANDZIC ◽  
J. PALECEK
Keyword(s):  
Spinal Cord ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Short Review ◽  
Pain Modulation ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Receptors ◽  
Transient Receptor ◽  
And Function

The structure, expression and function of the transient receptor potential vanilloid 1 (TRPV1) receptor were intensively studied since the cloning in 1997 and TRPV1 receptors are now considered to act as transducers and molecular integrators of nociceptive stimuli in the periphery. In contrast, spinal TRPV1 receptors were studied less extensively and their role in pain modulation is still not fully understood. This short review is a follow up on our previous summary in this area (Spicarova and Palecek 2008). The aim was to review preferentially the most recent findings concerning the role of the spinal TRPV1 receptors, published within the last five years. The update is given on the expression and function of the spinal TRPV1 receptors, their activation by endogenous agonists, interaction between the endocannabinoid and endovanillod system and possible role of the spinal TRPV1 receptors in pathological pain states. There is now mounting evidence that TRPV1 receptors may be an important element in modulation of nociceptive information at the spinal cord level and represent an interesting target for analgesic therapy.

Activation of transient receptor potential vanilloid subtype 1 increases secretion of the hypofunctional, transplanted submandibular gland

2010 ◽  
Vol 299 (1) ◽  
pp. G54-G62 ◽  
Author(s):  
Y. Zhang ◽  
X. Cong ◽  
L. Shi ◽  
B. Xiang ◽  
Y. M. Li ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Submandibular Gland ◽  
Transient Receptor Potential ◽  
Keratoconjunctivitis Sicca ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Dependent Manner ◽  
Aquaporin 5 ◽  
Gland Cells ◽  
Transient Receptor

Hyposecretion occurs in most patients early after submandibular gland autotransplantation for severe keratoconjunctivitis sicca. Endogenous transient receptor potential vanilloid subtype 1 (TRPV1) has been recently demonstrated in rabbit submandibular glands, and activation of TRPV1 by capsaicin increases secretion in isolated glands, but the TRPV1-mediated secretory mechanism remains to be elucidated. The purpose of this study was to verify whether activation of TRPV1 by capsaicin could improve the secretion of transplanted gland and its underlying mechanism. The salivary flow of the transplanted glands was significantly decreased, and the mRNA and protein levels of TRPV1 and aquaporin 5 (AQP5) were downregulated in the transplanted glands. Topical capsaicin cream increased secretion and upregulated levels of TRPV1 and AQP5 in transplanted glands. Moreover, in cultured submandibular gland cells, capsaicin increased the mRNA expression of AQP5 and led to redistribution of AQP5 from the cytoplasm to the plasma membrane via TRPV1 activation. Capsaicin enhanced the phosphorylation of extracellular signal-regulated kinase (ERK). Preincubation of cells with PD98059, an inhibitor of ERK kinase, suppressed the capsaicin-induced mRNA expression of AQP5. In summary, the capsaicin-induced secretory mechanism involved activation of TRPV1 and upregulation of AQP5 in an ERK-dependent manner and promoted the redistribution of AQP5 in submandibular gland cells. Activation of TRPV1 may provide a new therapeutic strategy to improve submandibular gland hypofunction.

scholarly journals Targeting TRPV3 for the Development of Novel Analgesics

2013 ◽  
Vol 6 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Susan M. Huang ◽  
Man-Kyo Chung
Keyword(s):  
Pain Perception ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Pharmaceutical Companies ◽  
Transient Receptor Potential Vanilloid ◽  
Potential Development ◽  
Transient Receptor ◽  
And Function ◽  
Distinct Features

Decades of characterization of the transient receptor potential vanilloid subtype 1 (TRPV1) have led to the realization of its central role in thermosensation and pain perception. A large number of pharmaceutical companies have had interest in developing TPRV1 antagonists for the treatment of pain. The subsequent discovery of multiple other members of this TRPV family has not gone unnoticed. TRPV3 exhibits approximately 40% homology to TRPV1, and has common as well as distinct features from TRPV1 in channel physiology, expression and function. Here we review the current understanding of TRPV3 channel biology, activation, sensitization and the consequences of TRPV3 manipulation for thermosensation and nociception, as well as additional considerations regarding the expression of TRPV3 in the skin. We weigh in on the available evidence in the context of potential development of TRPV3 modulating agents as analgesics.

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