Transient Receptor Potential Vanilloid Cation Research Articles

Capsaicin inhibits intestinal Cl- secretion and promotes Na+ absorption by blocking TRPV4 channels in healthy and colitic mice

Although capsaicin has been studied extensively as an activator of the transient receptor potential vanilloid cation channel subtype 1 (TRPV1) channels in sensory neurons, little is known about its TRPV1-independent actions in gastrointestinal health and disease. Here, we aimed to investigate the pharmacological actions of capsaicin as a food additive and medication on intestinal ion transporters in mouse models of ulcerative colitis (UC). The short-circuit current (Isc) of the intestine from WT, TRPV1-, and TRPV4-KO mice were measured in Ussing chambers, and Ca2+ imaging was performed on small intestinal epithelial cells. We also performed Western blots, immunohistochemistry, and immunofluorescence on intestinal epithelial cells and on intestinal tissues following UC induction with dextran sodium sulfate. We found that capsaicin did not affect basal intestinal Isc but significantly inhibited carbachol- and caffeine-induced intestinal Isc in WT mice. Capsaicin similarly inhibited the intestinal Isc in TRPV1 KO mice, but this inhibition was absent in TRPV4 KO mice. We also determined that Ca2+ influx via TRPV4 was required for cholinergic signaling–mediated intestinal anion secretion, which was inhibited by capsaicin. Moreover, the glucose-induced jejunal Iscvia Na+/glucose cotransporter was suppressed by TRPV4 activation, which could be relieved by capsaicin. Capsaicin also stimulated ouabain- and amiloride-sensitive colonic Isc. Finally, we found that dietary capsaicin ameliorated the UC phenotype, suppressed hyperaction of TRPV4 channels, and rescued the reduced ouabain- and amiloride-sensitive Isc. We therefore conclude that capsaicin inhibits intestinal Cl- secretion and promotes Na+ absorption predominantly by blocking TRPV4 channels to exert its beneficial anti-colitic action.

Hereditary sensory motor polyneuropathy

Background. Congenital contractures are a heterogeneous group of diseases with different prognosis and different treatment modalities. Clinical case. This article describes a family case of hereditary sensory motor polyneuropathy caused by the mutation of с.943G>A (р.Arg315Trp) in the transient receptor potential vanilloid cation channel 4 ( TRPV4 ) (NM_021625.4). The patient’s clinical and neurological characteristics as well as the results of genetic and neurophysiological examinations are presented. Discussion. Most often, mutations in the TRPV4 lead to 3 main diseases: autosomal dominant hereditary sensory motor neuropathy, type 2C, scapuloperoneal spinal muscular atrophy, and congenital non-progressive distal spinal muscular atrophy with contractures. The present article describes in detail the differential diagnosis of hereditary sensory motor polyneuropathy to facilitate accurate verification of this disease by clinicians. Conclusion. Patients with congenital multiple contractures need cooperative observation and examination by orthopedic surgeons and neurologists, including neurophysiological and genetic interventions in the examination plan for disease verification in order to optimize the treatment strategy and to predict the outcomes.

Febrile temperature change modulates CD4 T cell differentiation via a TRPV channel-regulated Notch-dependent pathway

Fever is a conserved and prominent response to infection. Yet, the issue of how CD4 T cell responses are modulated if they occur at fever temperatures remains poorly addressed. We have examined the priming of naive CD4 T cells in vitro at fever temperatures, and we report notable fever-mediated modulation of their cytokine commitment. When naive CD4 T cells were primed by plate-bound anti-CD3 and anti-CD28 monoclonal antibodies at moderate fever temperature (39 °C), they enhanced commitment to IL4/5/13 (Th2) and away from IFNg (Th1). This was accompanied by up-regulation of the Th2-relevant transcription factor GATA3 and reduction in the Th1-relevant transcription factor Tbet. Fever sensing by CD4 T cells involved transient receptor potential vanilloid cation channels (TRPVs) since TRPV1/TRPV4 antagonism blocked the febrile Th2 switch, while TRPV1 agonists mediated a Th2 switch at 37 °C. The febrile Th2 switch was IL4 independent, but a γ-secretase inhibitor abrogated it, and it was not found in Notch1-null CD4 T cells, identifying the Notch pathway as a major mediator. However, when naive CD4 T cells were primed via antigen and dendritic cells (DCs) at fever temperatures, the Th2 switch was abrogated via increased production of IL12 from DCs at fever temperatures. Thus, immune cells directly sense fever temperatures with likely complex physiological consequences.

Localized Excitation of Neural Activity via Rapid Magnetothermal Drug Release

Hysteretic heat dissipation by magnetic nanoparticles (MNPs) in alternating magnetic fields (AMFs) allows these materials to act as local transducers of external stimuli. Commonly employed in cancer research, MNPs have recently found applications in remote control of heat‐dependent cellular pathways. Here, a thermally labile linker chemistry is adapted for the release of neuromodulatory compounds from the surfaces of MNPs via local nanoscale heating. By examining a range of MNP sizes, and considering individual particle loss powers, AMF conditions and nanomaterials suitable for rapid and complete release of a payload from MNP surfaces are selected. Local release of allyl isothiocyanate, an agonist of the Ca2+ channel TRPV1 (transient receptor potential vanilloid cation channel subfamily member 1), from iron oxide MNPs results in pharmacological excitation of neurons with latencies of ≈12 s. When targeted to neuronal membranes, these MNPs trigger Ca2+ influx and action potential firing at particle concentrations three orders of magnitude less than those previously used for magnetothermal neuromodulation accomplished with bulk heating.

Retracted: α,β‐Unsaturated aldehyde pollutant acrolein suppresses cardiomyocyte contractile function: Role of TRPV1 and oxidative stress

Air pollution is associated with an increased prevalence of heart disease and is known to trigger a proinflammatory response via stimulation of transient receptor potential vanilloid cation channels (TRPV1, also known as the capsaicin receptor). This study was designed to examine the effect of acrolein, an essential α,β-unsaturated aldehyde pollutant, on myocardial contractile function and the underlying mechanism involved with a focus on TRPV1 and oxidative stress. Cardiomyocyte mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix MyoCam® system including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90 ), fura-2 fluorescence intensity (FFI) and intracellular Ca(2+) decay. Changes in apoptosis and TRPV1 were evaluated using Western blot analysis. The degree of oxidative stress was assessed using the ratio between reduced and oxidized glutathione. Results obtained revealed that exposure of cardiomyocytes to acrolein acutely compromised contractile and intracellular Ca(2+) properties including depressed PS, ± dL/dt and ΔFFI, as well as prolonged TR90 and intracellular Ca(2+) decay. In addition, acrolein exposure upregulated TRPV1 associated with an increase in both apoptosis and oxidative stress. However, the acrolein-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, as well as apoptosis (as evidenced by Bcl-2, Bax, FasL, Caspase-3 and -8), were negated by the reactive oxygen species (ROS) scavenger glutathione or the TRPV1 antagonist capsazepine. Collectively these data suggest that the α,β-unsaturated aldehyde pollutant acrolein may play a role in the pathogenesis and sequelae of air pollution-induced heart disease via a TRPV1- and oxidative stress-dependent mechanism.

Influence of temperature on urethra to bladder micturition reflex in the awake ewe

The flow of fluid along the urethra is known to facilitate detrusor contraction during micturition. This reflex, previously described in awake ewes, helps to achieve complete bladder emptying. In anesthetized cats, another urethra to bladder reflex involving urethral cold receptors has been described. The aim of this study was to investigate whether the urethral reflex first described in awake ewes could also be temperature-dependent. Experiments were performed on 10 healthy ewes. Urethral flows were performed by injecting 10 ml saline (ranging from 17 to 43 degrees C) at the level of the proximal urethra. Catheterization of the bladder was performed so that detrusor pressure was continually recorded during the experiments. Urethral flows using body temperature saline (37-39 degrees C) consistently evoked detrusor contraction. Urethral flows using saline at temperatures between 40 and 43 degrees C induced detrusor contractions that were not significantly different from those observed at 37-39 degrees C. Urethral flows using saline at temperatures below 37-39 degrees C (17-36 degrees C) resulted in a weaker or absent detrusor contraction. In ewes, we have shown that urethral to bladder micturition reflex involving mechanoreceptors is decreased at temperatures below the physiological range. It is suggested that transient receptor potential vanilloid cation channels (e.g., TRPV4 which is activated by sheer/stress flows at near-body temperature) could be involved in this urethra to bladder reflex. In humans, this reflex has hardly been described and is still a matter of debate. Our results reinforce that its full investigation may require systematic use of a range of saline flows at different temperatures.