5-Iodoresiniferatoxin Evokes Hypothermia in Mice and Is a Partial Transient Receptor Potential Vanilloid 1 Agonist in Vitro

2005 ◽  
Vol 314 (3) ◽  
pp. 1378-1385 ◽  
Author(s):  
Isao Shimizu ◽  
Tohko Iida ◽  
Nobuhiko Horiuchi ◽  
Michael J. Caterina
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

scholarly journals Novel role of transient receptor potential vanilloid 2 in the regulation of cardiac performance

2014 ◽  
Vol 306 (4) ◽  
pp. H574-H584 ◽  
Author(s):  
Jack Rubinstein ◽  
Valerie M. Lasko ◽  
Sheryl E. Koch ◽  
Vivek P. Singh ◽  
Vinicius Carreira ◽  
...  
Keyword(s):  
Vascular Function ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Wild Type ◽  
Transient Receptor ◽  
Systolic And Diastolic Function ◽  
Myocyte Contractility

Transient receptor potential cation channels have been implicated in the regulation of cardiovascular function, but only recently has our laboratory described the vanilloid-2 subtype (TRPV2) in the cardiomyocyte, though its exact mechanism of action has not yet been established. This study tests the hypothesis that TRPV2 plays an important role in regulating myocyte contractility under physiological conditions. Therefore, we measured cardiac and vascular function in wild-type and TRPV2−/− mice in vitro and in vivo and found that TRPV2 deletion resulted in a decrease in basal systolic and diastolic function without affecting loading conditions or vascular tone. TRPV2 stimulation with probenecid, a relatively selective TRPV2 agonist, caused an increase in both inotropy and lusitropy in wild-type mice that was blunted in TRPV2−/− mice. We examined the mechanism of TRPV2 inotropy/lusitropy in isolated myocytes and found that it modulates Ca2+ transients and sarcoplasmic reticulum Ca2+ loading. We show that the activity of this channel is necessary for normal cardiac function and that there is increased contractility in response to agonism of TRPV2 with probenecid.

scholarly journals Blockade of Transient Receptor Potential Vanilloid 4 Enhances Antioxidation after Myocardial Ischemia/Reperfusion

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Qiongfeng Wu ◽  
Kai Lu ◽  
Zhaoyang Zhao ◽  
Binbin Wang ◽  
Huixia Liu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Transient Receptor Potential ◽  
Ischemia Reperfusion ◽  
Receptor Potential ◽  
Nuclear Accumulation ◽  
Transient Receptor Potential Vanilloid ◽  
Antioxidative Stress ◽  
Transient Receptor ◽  
Myocardial Ischemia Reperfusion

Antioxidative stress provides a cardioprotective effect during myocardial ischemia/reperfusion (I/R). Previous research has demonstrated that the blockade of transient receptor potential vanilloid 4 (TRPV4) attenuates myocardial I/R injury. However, the underlying mechanism remains unclear. The current study is aimed at investigating the antioxidative activity of TRPV4 inhibition and elucidating the underlying mechanisms in vitro and ex vivo. We found that the inhibiting TRPV4 by the selective TRPV4 blocker HC-067047 or specific TRPV4-siRNA significantly reduces reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA) levels in H9C2 cells exposed to hypoxia/reoxygenation (H/R). Meanwhile, the activity of antioxidative enzymes, particularly superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), is enhanced. Furthermore, after H/R, HC-067047 treatment increases the expression of P-Akt and the translocation of nuclear factor E2-related factor 2 (Nrf2) and related antioxidant response element (ARE) mainly including SOD, GSH-Px, and catalase (CAT). LY294002, an Akt inhibitor, suppresses HC-067047 and specific TRPV4-siRNA-induced Nrf2 expression and its nuclear accumulation. Nrf2 siRNA attenuates HC-067047 and specific TRPV4-siRNA-induced ARE expression. In addition, treatment with LY294002 or Nrf2 siRNA significantly attenuates the antioxidant and anti-injury effects of HC-067047 in vitro. Finally, in experiments on isolated rat hearts, we confirmed the antioxidative stress roles of TRPV4 inhibition during myocardial I/R and the application of exogenous H2O2. In conclusion, the inhibition of TRPV4 exerts cardioprotective effects through enhancing antioxidative enzyme activity and expressions via the Akt/Nrf2/ARE pathway.

Soluble α-klotho anchors TRPV5 to the distal tubular cell membrane independent of FGFR1 by binding TRPV5 and galectin-1 simultaneously

2021 ◽  
Author(s):  
Jinho Lee ◽  
Kyung Don Ju ◽  
Hyo Jin Kim ◽  
Bodokhsuren Tsogbadrakh ◽  
Hyunjin Ryu ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Distal Tubule ◽  
Transient Receptor Potential Vanilloid ◽  
Calcium Excretion ◽  
Tubular Cells ◽  
Calcium Reabsorption ◽  
Transient Receptor

Hypercalciuria is one of early manifestations of diabetic nephropathy (DN). This is partially due to a decrease in the expression of renal transient receptor potential vanilloid type 5 (TRPV5), which is responsible for renal calcium reabsorption. Soluble klotho was previously determined to increase TRPV5 by cleaving sialic acid, causing TRPV5 to bind to membrane protein galectin-1. However, a recent study showed that soluble klotho binds to α2-3-sialyllactose - where sialic acid is located - on TRPV5, rather than cleave it. Here, we report that soluble klotho tethers TRPV5 on the membrane by binding both TRPV5 and galectin-1, thereby protecting membrane TRPV5 from diabetes-induced endocytosis. We injected recombinant soluble α-klotho protein (rKL) into db/db and db/m mice for 8 weeks and collected urine and the kidney. We administered rKL, AZD4547 (FGFR1 inhibitor), and OTX008 (Galectin 1 inhibitor) to cultured mouse distal tubular cells, with or without 30 mM high glucose (HG) exposure. db/db mice showed increased renal calcium excretion and decreased renal TRPV5 expression. rKL treatment reversed this change. In vitro, TRPV5 expression in distal tubular cells decreased under HG conditions, and rKL successfully upregulated TRPV5 with or without FGF23. Also, immunofluorescence showed co-localization of klotho, TRPV5, and galectin-1 in distal tubule cells, suggesting that klotho binds to both TRPV5 and galectin 1. Moreover, when both FGFR1 and galectin-1 were inhibited, rKL failed to increase TRPV5 under HG conditions. Our results indicate that soluble klotho prevents TRPV5 from degradation and subsequent diabetes-induced endocytosis by anchoring TRPV5 through binding with both TRPV5 and galectin-1.

scholarly journals Pirt Together with TRPV1 Is Involved in the Regulation of Neuropathic Pain

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Changming Wang ◽  
Leying Gu ◽  
Yonglan Ruan ◽  
Tana Gegen ◽  
Lei Yu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Transient Receptor Potential ◽  
Life Quality ◽  
Thermal Hyperalgesia ◽  
In Vitro Study ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Cci Model ◽  
Transient Receptor

Neuropathic pain is a chronic pain and reduces the life quality of patients substantially. Transient receptor potential vanilloid channel 1 (TRPV1), a nonselective cation channel, has been shown to play a crucial role in neuropathic pain. Although TRPV1 plays an important role in neuropathic pain, the mechanism of how TRPV1 was regulated in neuropathic pain remains unclear. Pirt is a membrane protein and binds to TRPV1 to enhance its activity. It was suggested that Pirt should also be involved in neuropathic pain. In this study, we investigated the role of Pirt in neuropathic pain (CCI model); the results show that mechanical allodynia and thermal hyperalgesia were alleviated in Pirt−/− mice in CCI models. TRPV1 expression was increased by immunofluorescence and real-time PCR experiments. The increase in TRPV1 expression was less in Pirt knockout mice in CCI models. Moreover, the number of capsaicin-responding neurons and the magnitude of evoked calcium response were attenuated in DRG neurons from Pirt−/− mice in CCI models. Finally, we found that the pain behavior attenuated in dysfunction of both Pirt and TRPV1 was much stronger than in dysfunction of Pirt or TRPV1 only in a CCI model in vitro study. Taken together, Pirt together with TRPV1 is involved in CCI-induced neuropathic pain.

scholarly journals A TRPV2–PKA Signaling Module for Transduction of Physical Stimuli in Mast Cells

2004 ◽  
Vol 200 (2) ◽  
pp. 137-147 ◽  
Author(s):  
Alexander J. Stokes ◽  
Lori M.N. Shimoda ◽  
Murielle Koblan-Huberson ◽  
Chaker N. Adra ◽  
Helen Turner
Keyword(s):  
Mast Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Functional Coupling ◽  
Transient Receptor Potential Vanilloid ◽  
Functional Responses ◽  
Signaling Mechanism ◽  
Cutaneous Mast Cell ◽  
Transient Receptor

Cutaneous mast cell responses to physical (thermal, mechanical, or osmotic) stimuli underlie the pathology of physical urticarias. In vitro experiments suggest that mast cells respond directly to these stimuli, implying that a signaling mechanism couples functional responses to physical inputs in mast cells. We asked whether transient receptor potential (vanilloid) (TRPV) cation channels were present and functionally coupled to signaling pathways in mast cells, since expression of this channel subfamily confers sensitivity to thermal, osmotic, and pressure inputs. Transcripts for a range of TRPVs were detected in mast cells, and we report the expression, surface localization, and oligomerization of TRPV2 protein subunits in these cells. We describe the functional coupling of TRPV2 protein to calcium fluxes and proinflammatory degranulation events in mast cells. In addition, we describe a novel protein kinase A (PKA)–dependent signaling module, containing PKA and a putative A kinase adapter protein, Acyl CoA binding domain protein (ACBD)3, that interacts with TRPV2 in mast cells. We propose that regulated phosphorylation by PKA may be a common pathway for TRPV modulation.

Sign in / Sign up

Export Citation Format

Share Document