(R)-(5-tert-Butyl-2,3-dihydro-1H-inden-1-yl)-3-(1H-indazol-4-yl)-urea (ABT-102) Blocks Polymodal Activation of Transient Receptor Potential Vanilloid 1 Receptors in Vitro and Heat-Evoked Firing of Spinal Dorsal Horn Neurons in Vivo

2008 ◽  
Vol 326 (3) ◽  
pp. 879-888 ◽  
Author(s):  
Carol S. Surowy ◽  
Torben R. Neelands ◽  
Bruce R. Bianchi ◽  
Steve McGaraughty ◽  
Rachid El Kouhen ◽  
...  
Keyword(s):  
Spinal Dorsal Horn ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Spinal Dorsal Horn Neurons ◽  
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 Effect of resolvins on sensitisation of TRPV1 and visceral hypersensitivity in IBS

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321530
Author(s):  
Eluisa Perna ◽  
Javier Aguilera-Lizarraga ◽  
Morgane V Florens ◽  
Piyush Jain ◽  
Stavroula A Theofanous ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Visceral Hypersensitivity ◽  
Transient Receptor Potential Vanilloid ◽  
Drg Neurons ◽  
Somatic Pain ◽  
Protein Receptor ◽  
Transient Receptor

ObjectiveResolvins (RvD1, RvD2 and RvE1) are endogenous anti-inflammatory lipid mediators that display potent analgesic properties in somatic pain by modulating transient receptor potential vanilloid 1 (TRPV1) activation. To what extent these molecules could also have a beneficial effect on TRPV1 sensitisation and visceral hypersensitivity (VHS), mechanisms involved in IBS, remains unknown.DesignThe effect of RvD1, RvD2 and RvE1 on TRPV1 activation and sensitisation by histamine or IBS supernatants was assessed on murine dorsal root ganglion (DRG) neurons using live Ca2+ imaging. Based on the results obtained in vitro, we further studied the effect of RvD2 in vivo using a murine model of post-infectious IBS and a rat model of post-inflammatory VHS. Finally, we also tested the effect of RvD2 on submucosal neurons in rectal biopsies of patients with IBS.ResultsRvD1, RvD2 and RvE1 prevented histamine-induced TRPV1 sensitisation in DRG neurons at doses devoid of an analgesic effect. Of note, RvD2 also reversed TRPV1 sensitisation by histamine and IBS supernatant. This effect was blocked by the G protein receptor 18 (GPR18) antagonist O-1918 (3–30 µM) and by pertussis toxin. In addition, RvD2 reduced the capsaicin-induced Ca2+ response of rectal submucosal neurons of patients with IBS. Finally, treatment with RvD2 normalised pain responses to colorectal distention in both preclinical models of VHS.ConclusionsOur data suggest that RvD2 and GPR18 agonists may represent interesting novel compounds to be further evaluated as treatment for IBS.

scholarly journals Adipose-derived exosomes impairs endothelial transient receptor potential vanilloid 4 channels and elevates blood pressure in abdominal obesity

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J Wan ◽  
S Liu ◽  
Y Yang ◽  
D Wang ◽  
F Ran ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Abdominal Obesity ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Endothelial Barrier ◽  
Transient Receptor Potential Vanilloid ◽  
Induced Hypertension ◽  
Transient Receptor

Abstract Aim Large epidemiological studies have found that abdominal obesity is a strong risk factor for hypertension. Impaired endothelium-dependent vasodilation is a hallmark of obesity-induced hypertension. Adipose-derived exosomes can regulate distant tissues as novel adipokines, providing a new mechanism for cell-cell interactions. However, the effects of adipose-derived exosomes on obesity-induced hypertension are unknown. Methods We extracted three adipose-derived exosomes, including high-fat diet (HFD) mouse serum exosome, adipose tissue exosome, and adipose-derived stem cell exosome, and further explored their effects on endothelium-dependent vasodilation in vivo and in vitro. Results Impairment of endothelial transient receptor potential vanilloid 4 (TRPV4) channel activity and vasodilation were observed in the arteries from abdominal obesity patients. Ca2+ influx through TRPV4 channels at myoendothelial projections to smooth muscle cells decreases resting blood pressure in nonobese mice, a response that is diminished in HFD mice. Administration of three exosomes elevated blood pressure by promoting artery endothelial barrier permeability, impairing the expression of adherens junctions, and aggravating inflammatory response in vivo and in vitro, accompanied by TRPV4/Ca2+ pathway inhibition. Conclusions Impairment of endothelial TRPV4 channels contributes to obesity-induced hypertension and imply that HFD-induced obesity plays a role in blood pressure by aggravating the artery endothelial barrier injury and inflammatory response via adipose-derived exosomes, at least partially, through inhibiting the TRPV4/Ca2+ pathway. FUNDunding Acknowledgement Type of funding sources: None. Main funding source(s): This research was supported by grants from the National Natural Science Foundation of China (81970262) (P.J.W.), Innovation Team Project Department of Education of Sichuan Province (18TD0030) (PJW), Central Funds Guiding the Local Science and Technology Development of Sichuan Province (2020ZYD036, P.W.), and grants from the Scientific Research Fund of Chengdu Medical College (CYZYB20-07) (J.W.).

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