scholarly journals Transient Receptor Potential Vanilloid Subtype 1 Mediates Cell Death of Mesencephalic Dopaminergic Neurons In Vivo and In Vitro

2005 ◽  
Vol 25 (3) ◽  
pp. 662-671 ◽  
Author(s):  
S. R. Kim
Keyword(s):  
Cell Death ◽  
Dopaminergic Neurons ◽  
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 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.).

scholarly journals The Quaternary Lidocaine Derivative, QX-314, Exerts Biphasic Effects on Transient Receptor Potential Vanilloid Subtype 1 Channels In Vitro 

2011 ◽  
Vol 114 (6) ◽  
pp. 1425-1434 ◽  
Author(s):  
Ricardo E. Rivera-Acevedo ◽  
Stephan A. Pless ◽  
Christopher A. Ahern ◽  
Stephan K. W. Schwarz
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Xenopus Laevis Oocytes ◽  
Sensory Blockade ◽  
Nociceptive Neurons ◽  
Trpv1 Channels ◽  
Transient Receptor

Background Transient receptor potential vanilloid subfamily member 1 (TRPV1) channels are important integrators of noxious stimuli with pronounced expression in nociceptive neurons. The experimental local anesthetic, QX-314, a quaternary (i.e., permanently charged) lidocaine derivative, recently has been shown to interact with and permeate these channels to produce nociceptive and sensory blockade in animals in vivo. However, little is known about the specific interactions between QX-314 and TRPV1 channels. Thus, the authors examined the mechanistic basis by which QX-314 acts on TRPV1 channels. Methods The authors conducted an in vitro laboratory study in which they expressed TRPV1 and TRPV4 channels in Xenopus laevis oocytes and recorded cation currents with the two-electrode voltage clamp method. They used confocal microscopy for Ca²⁺ imaging in TRPV1 transient transfected tsA201 cells. Drugs were bath-applied by gravity perfusion. Statistical analyses were performed using Student t test, ANOVA, and post tests as appropriate (P < 0.05). Results QX-314 activated TRPV1 channels at 10, 30, and 60 mM (0.4 ± 0.1%, 3.5 ± 1.3%, and 21.5 ± 6.9% of normalized peak activation, respectively; mean ± SEM; n = 12) but not TRPV4 channels (P < 0.001). Activation by QX-314 was blocked by the TRPV1 antagonist, capsazepine (100 μM). QX-314 (60 mM) activation and blockade by capsazepine was also demonstrated in Ca²⁺ imaging studies on TRPV1-expressing tsA201 cells. At subactivating concentrations (less than 1 mM), QX-314 potently inhibited capsaicin-evoked TRPV1 currents with an IC₅₀ of 8.0 ± 0.6 μM. Conclusions The results of this study show that the quaternary lidocaine derivative QX-314 exerts biphasic effects on TRPV1 channels, inhibiting capsaicin-evoked TRPV1 currents at lower (micromolar) concentrations and activating TRPV1 channels at higher (millimolar) concentrations. These findings provide novel insights into the interactions between QX-314 and TRPV1 and may provide an explanation for the irritant properties of intrathecal QX-314 in mice in vivo.

scholarly journals Hypernatremia-induced vasopressin secretion is not altered in TRPV1−/− rats

2016 ◽  
Vol 311 (3) ◽  
pp. R451-R456 ◽  
Author(s):  
Andrew Blake Tucker ◽  
Sean D. Stocker
Keyword(s):  
Intravenous Injection ◽  
Transient Receptor Potential ◽  
Plasma Osmolality ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channels ◽  
Vasopressin Secretion ◽  
Transient Receptor

Changes in osmolality or extracellular NaCl concentrations are detected by specialized neurons in the hypothalamus to increase vasopressin (VP) and stimulate thirst. Recent in vitro evidence suggests this process is mediated by an NH2-terminal variant of the transient receptor potential vanilloid type 1 (TRPV1) channel expressed by osmosensitive neurons of the lamina terminalis and vasopressinergic neurons of the supraoptic nucleus. The present study tested this hypothesis in vivo by analysis of plasma VP levels during acute hypernatremia in awake control and TRPV1−/− rats. TRPV1−/− rats were produced by a Zinc-finger-nuclease 2-bp deletion in exon 13. Intravenous injection of the TRPV1 agonist capsaicin produced hypotension and bradycardia in control rats, but this response was absent in TRPV1−/− rats. Infusion of 2 M NaCl (1 ml/h iv) increased plasma osmolality, electrolytes, and VP levels in both control and TRPV1−/− rats. However, plasma VP levels did not differ between strains at any time. Furthermore, a linear regression between plasma VP versus osmolality revealed a significant correlation in both control and TRPV1−/− rats, but the slope of the regression lines was not attenuated in TRPV1−/− versus control rats. Hypotension produced by intravenous injection of minoxidil decreased blood pressure and increased plasma VP levels similarly in both groups. Finally, both treatments stimulated thirst; however, cumulative water intakes in response to hypernatremia or hypotension were not different between control and TRPV1−/− rats. These findings suggest that TRPV1 channels are not necessary for VP secretion and thirst stimulated by hypernatremia.

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