scholarly journals Sperm Cholesterol Content Modifies Sperm Function and TRPV1-Mediated Sperm Migration

2021 ◽  
Vol 22 (6) ◽  
pp. 3126
Author(s):  
Luca De Toni ◽  
Iva Sabovic ◽  
Vincenzo De Filippis ◽  
Laura Acquasaliente ◽  
Daniele Peterle ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Consensus Sequence ◽  
Specific Interaction ◽  
Receptor Potential ◽  
Human Sperm ◽  
Transient Receptor Potential Channels ◽  
Sperm Function ◽  
Dependent Manner ◽  
Sperm Migration ◽  
Dose Dependent

Transient receptor potential channels-vanilloid receptor 1 (TRPV1) regulates thermotaxis in sperm-oriented motility. We investigated the role of membrane cholesterol (Chol) on TRPV1-mediated human sperm migration. Semen samples were obtained from five normozoospemic healthy volunteers. Sperm membrane Chol content, quantified by liquid chromatography-mass spectrometry, was modified by incubating cells with 2-hydroxypropyl-ß-cyclodextrin (CD) or the complex between CD and Chol (CD:Chol). The effect on sperm migration on a 10 μM capsaicin gradient (CPS), a TRPV1 agonist, was then investigated. Motility parameters were evaluated by Sperm Class Analyser. Intracellular calcium concentration and acrosome reaction were measured by staining with calcium orange and FITC-conjugated anti-CD46 antibody, respectively. TRPV1-Chol interaction was modelled by computational molecular-modelling (MM). CD and CD:Chol, respectively, reduced and increased membrane Chol content in a dose-dependent manner, resulting in a dose-dependent increase and reduction of sperm migration in a CPS gradient. MM confirmed a specific interaction of Chol with a TRPV1 domain that appeared precluded to the Chol epimer epicholesterol (Epi-Chol). Accordingly, CD:Epi-Chol was significantly less efficient than CD:Chol, in reducing sperm migration under CPS gradient. Chol inhibits TRPV1-mediated sperm function by directly interacting with a consensus sequence of the receptor.

Substance P Evokes Cation Currents Through TRP Channels in HEK293 Cells

2003 ◽  
Vol 90 (3) ◽  
pp. 2069-2073 ◽  
Author(s):  
E. J. Oh ◽  
T. D. Gover ◽  
R. Cordoba-Rodriguez ◽  
D. Weinreich
Keyword(s):  
Substance P ◽  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Hek293 Cells ◽  
Dependent Manner ◽  
Primary Sensory Neurons ◽  
Potential Channels

Activation of any of the three known tachykinin receptors (NK1R, -2R, or -3R) can cause a rise in [Ca2+]i via a pertussis toxin-insensitive heterotrimeric G protein, Gq/G11, activation of phospholipase C (PLC), and a membrane depolarization. Tachykinins can depolarize neurons by two distinct mechanisms: 1) they reduce a resting K+ current in many neurons or 2) in parasympathetic and vagal primary sensory neurons, they activate a nonspecific cation current ( Icat). Transient receptor potential channels (TRPC) are nonspecific cation channels that can be activated by a rise in [Ca2+]i in a PLC-dependent manner. The present work tests whether NK2R can signal TRPC. We applied standard whole cell patch-clamp recordings to HEK293 cells stably transfected with the human TRP3 channels (TRP3C), and transiently transfected with a functional NK2R-EGFP. Bath applied Substance P (SP, 1 μM) induced an Icat in the cells expressing both TRP3C and NK2R. Icat reached its peak value in approximately 3 min (195 ± 120.0 s, mean ± SE, n = 20), had a peak density of 11.3 ± 3.48 pA/pF ( n = 24), and was blocked by an NK2R-specific antagonist (SR48968, 100 nM). The Erev value for the SP current was 6.8 ± 7.66 mV ( n = 6), suggestive of a nonspecific cation channel. Icat was not measurable in TRP3C-expressing HEK293 cells without NK2R expression ( n = 6) or in wild-type HEK293 cells with NK2R expression ( n = 12). These data indicate that NK2R can be functionally coupled to TRP channels in HEK293 cells and suggest that SP-induced cation currents in vagal primary sensory neurons might be mediated by TRPC.

Abstract 39: The Transient Receptor-Potential Channel 6 Regulates Thromboxane A2 Receptor-Operated Calcium Entry and Plays a Critical Role in Platelet Function

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Fadi T Khasawneh ◽  
Enma V Espinosa ◽  
Olivia A Lin ◽  
John P Murad
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Transient Receptor Potential ◽  
Critical Role ◽  
Receptor Potential ◽  
Underlying Mechanism ◽  
Calcium Entry ◽  
Transient Receptor Potential Channels ◽  
Dependent Manner ◽  
Transient Receptor

Although changes in the intracellular levels of calcium is a central step in platelet activation, the underlying mechanism of changes that are dependent on receptor-operated calcium entry (ROCE) remains to be defined. Furthermore, it was proposed, though never proven, that the Transient Receptor-Potential Channels (TRPCs) may play a key role in this process. In this connection, we have previously shown that TRPC6 plays a vital role in physiological hemostasis and thrombogenesis. However, the underlying mechanism by which TRPC6 modulates these processes also remains to be determined. Based on these considerations, we hypothesized that TRPC6 plays an essential role in ROCE and hence platelet function. Using a (genetic) TRPC6 knockout (KO) mouse approach, our preliminary studies revealed that these platelets exhibited a defect in platelet aggregation induced by the thromboxane A 2 receptor (TPR) agonist U46619. Conversely, the aggregation response triggered by ADP or the thrombin receptor activating peptide 4 (TRAP4) was found to be comparable to that of the wild-type (WT) platelets. Separate studies revealed that the TRPC6 deficient platelets were also found to exhibit a defect in TPR-mediated dense granule (ATP) secretion, whereas that of ADP and TRAP4 was normal. Moreover, we observed a defect in integrin GP IIb-IIIa activation that was again specific to TPR (normal activation in response to ADP and TRAP4), suggesting a defect in inside-out signaling. Finally, TPR-dependent CE was also found to be deficient in the TRPC6 KO platelets, unlike that stimulated by ADP or TRAP4. Future studies will further investigate the molecular mechanism of TRPC6-regulated platelet function and CE. Taken together, these findings demonstrate for the first time that TRPC6 regulates CE in a TPR-dependent manner and that this regulation consequently modulates platelet aggregation, secretion, as well as GP IIb-IIIa activation. These studies may define a new therapeutic target for managing multiple thrombosis-based disorders.

scholarly journals TRPs in Tox: Involvement of Transient Receptor Potential-Channels in Chemical-Induced Organ Toxicity—A Structured Review

Cells ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 98 ◽  
Author(s):  
Dirk Steinritz ◽  
Bernhard Stenger ◽  
Alexander Dietrich ◽  
Thomas Gudermann ◽  
Tanja Popp
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Specific Interaction ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Organ Systems ◽  
Organ Specific ◽  
Specific Organ ◽  
Potential Channels ◽  
Transient Receptor

Chemicals can exhibit significant toxic properties. While for most compounds, unspecific cell damaging processes are assumed, a plethora of chemicals exhibit characteristic odors, suggesting a more specific interaction with the human body. During the last few years, G-protein-coupled receptors and especially chemosensory ion channels of the transient receptor potential family (TRP channels) were identified as defined targets for several chemicals. In some cases, TRP channels were suggested as being causal for toxicity. Therefore, these channels have moved into the spotlight of toxicological research. In this review, we screened available literature in PubMed that deals with the role of chemical-sensing TRP channels in specific organ systems. TRPA1, TRPM and TRPV channels were identified as essential chemosensors in the nervous system, the upper and lower airways, colon, pancreas, bladder, skin, the cardiovascular system, and the eyes. Regarding TRP channel subtypes, A1, M8, and V1 were found most frequently associated with toxicity. They are followed by V4, while other TRP channels (C1, C4, M5) are only less abundantly expressed in this context. Moreover, TRPA1, M8, V1 are co-expressed in most organs. This review summarizes organ-specific toxicological roles of TRP channels.

scholarly journals Aconitine Induces TRPV2-Mediated Ca2+ Influx through the p38 MAPK Signal and Promotes Cardiomyocyte Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Chunai Yang ◽  
Xiaoyan Zeng ◽  
Zhongfeng Cheng ◽  
Junbo Zhu ◽  
Yangshan Fu
Keyword(s):  
P38 Mapk ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Mapk Signaling ◽  
Cardiomyocyte Apoptosis ◽  
Dependent Manner ◽  
H9c2 Cardiomyocytes ◽  
Transient Receptor ◽  
Effective Component ◽  
Dose Dependent

Aconitine is the main effective component of traditional Chinese medicine Aconitum, which has been proved to have severe cardiovascular toxicity. The toxic effect of aconitine on cardiomyocytes is related to intracellular calcium overload, but the mechanism remains unclear. The aim of this study was to explore the mechanism of aconitine inducing intracellular Ca2+ overload and promoting H9c2 cardiomyocyte apoptosis through transient receptor potential cation channel subfamily V member 2 (TRPV2). After treated with different concentrations of aconitine, the level of cell apoptosis, intracellular Ca2+, and expression of p-p38 MAPK and TRPV2 of H9c2 cardiomyocytes were detected. The results showed that aconitine induced Ca2+ influx and H9c2 cardiomyocyte apoptosis in a dose-dependent manner and promoted p38 MAPK activation as well as TRPV2 expression and plasma membrane (PM) metastasis. siTRPV2, tranilast, and SB202190 reversed intracellular Ca2+ overload and H9c2 cardiomyocyte apoptosis induced by aconitine. These results suggested that aconitine promoted TRPV2 expression and PM metastasis through p38 MAPK signaling, thus inducing intracellular Ca2+ overload and cardiomyocyte apoptosis. Furthermore, TRPV2 is a potential molecular target for the treatment of aconitine poisoning.

scholarly journals TRPA1 triggers hyperalgesia and inflammation after tooth bleaching

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chang Chen ◽  
Xiansheng Huang ◽  
Wenqiang Zhu ◽  
Chen Ding ◽  
Piaopiao Huang ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Critical Role ◽  
Receptor Potential ◽  
Tooth Bleaching ◽  
Dependent Manner ◽  
Protein Levels ◽  
Solid Foundation ◽  
Transient Receptor ◽  
Dose Dependent ◽  
Bleaching Gels

AbstractHyperalgesia has become a major problem restricting the clinical application of tooth bleaching. We hypothesized that transient receptor potential ankyrin 1 (TRPA1), a pain conduction tunnel, plays a role in tooth hyperalgesia and inflammation after bleaching. Dental pulp stem cells were seeded on the dentin side of the disc, which was cut from the premolar buccal tissue, with 15% (90 min) or 40% (3 × 15 min) bleaching gel applied on the enamel side, and treated with or without a TRPA1 inhibitor. The bleaching gel stimulated intracellular reactive oxygen species, Ca2+, ATP, and extracellular ATP in a dose-dependent manner, and increased the mRNA and protein levels of hyperalgesia (TRPA1 and PANX1) and inflammation (TNFα and IL6) factors. This increment was adversely affected by TRPA1 inhibitor. In animal study, the protein levels of TRPA1 (P = 0.0006), PANX1 (P < 0.0001), and proliferation factors [PCNA (P < 0.0001) and Caspase 3 (P = 0.0066)] increased significantly after treated rat incisors with 15% and 40% bleaching gels as detected by immunohistochemistry. These results show that TRPA1 plays a critical role in sensitivity and inflammation after tooth bleaching, providing a solid foundation for further research on reducing the complications of tooth bleaching.

scholarly journals Role of transient receptor potential channels in regulating spermatozoa functions: A mini-review

2018 ◽  
pp. 1618-1623 ◽  
Author(s):  
Akshay Kumar ◽  
Abhishek Kumar Mishra ◽  
Dilip Kumar Swain ◽  
Vijay Singh ◽  
Sarvajeet Yadav ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Sperm Function ◽  
Calcium Dependent ◽  
Potential Channels ◽  
Transient Receptor

Flagellar navigation along the genital tract of male and female in spermatozoa is accomplished through a number of biological, physiological, biochemical, and electrophysiological alterations in spermatozoa. These alterations are highly precise, dynamic, and regulated through a number of ion channels along with their associated pathways. Beating of flagella along with intracellular metabolism of spermatozoa is associated with fluxing of Ca++ as well as release of Ca++ from different sources. Calcium fluxing through the spermatozoa is mediated through sperm-specific calcium channel and also through transient receptor potential (TRP) channels which are diversified multifamily of ion channels which are activated through a number of extracellular agents such as pH, temperature, chemicals, and pathogens. Research has shown the dynamic role of TRP channels in regulating sperm functions such as sperm chemotaxis, rheotaxis, thermotaxis, and eventually fertilization. Diversified forms of TRP and their involvement in regulation of sperm function opens new horizons of understanding of the sperm function and, in specific, issues related to infertility. This mini-review is an attempt to draw some insights into the action of TRP channels in regulating sperm fertility competence through both calcium-dependent and calcium-independent mechanisms.

scholarly journals Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 668
Author(s):  
Concetta Altamura ◽  
Maria Raffaella Greco ◽  
Maria Rosaria Carratù ◽  
Rosa Angela Cardone ◽  
Jean-François Desaphy
Keyword(s):  
Ovarian Cancer ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Critical Role ◽  
Gynecologic Cancer ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Platinum Resistance

Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment.

scholarly journals Intractable Itch in Atopic Dermatitis: Causes and Treatments

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 229
Author(s):  
Yoshie Umehara ◽  
Chanisa Kiatsurayanon ◽  
Juan Valentin Trujillo-Paez ◽  
Panjit Chieosilapatham ◽  
Ge Peng ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Atopic Dermatitis ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Clinical Problem ◽  
Transient Receptor Potential Channels ◽  
Protease Activated Receptors ◽  
H1 Antihistamines ◽  
Potential Channels

Itch or pruritus is the hallmark of atopic dermatitis and is defined as an unpleasant sensation that evokes the desire to scratch. It is also believed that itch is a signal of danger from various environmental factors or physiological abnormalities. Because histamine is a well-known substance inducing itch, H1-antihistamines are the most frequently used drugs to treat pruritus. However, H1-antihistamines are not fully effective against intractable itch in patients with atopic dermatitis. Given that intractable itch is a clinical problem that markedly decreases quality of life, its treatment in atopic dermatitis is of high importance. Histamine-independent itch may be elicited by various pruritogens, including proteases, cytokines, neuropeptides, lipids, and opioids, and their cognate receptors, such as protease-activated receptors, cytokine receptors, Mas-related G protein-coupled receptors, opioid receptors, and transient receptor potential channels. In addition, cutaneous hyperinnervation is partly involved in itch sensitization in the periphery. It is believed that dry skin is a key feature of intractable itch in atopic dermatitis. Treatment of the underlying conditions that cause itch is necessary to improve the quality of life of patients with atopic dermatitis. This review describes current insights into the pathophysiology of itch and its treatment in atopic dermatitis.

scholarly journals Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment

2021 ◽  
Vol 22 (2) ◽  
pp. 778
Author(s):  
Anna Stasiłowicz ◽  
Anna Tomala ◽  
Irma Podolak ◽  
Judyta Cielecka-Piontek
Keyword(s):  
Pharmacological Activity ◽  
Transient Receptor Potential ◽  
Cannabis Sativa ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Raw Material ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes. The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson’s disease, Tourette’s syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors. The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood–brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.

scholarly journals Potentiation of TRPC5 by Protons

2007 ◽  
Vol 282 (46) ◽  
pp. 33868-33878 ◽  
Author(s):  
Marcus Semtner ◽  
Michael Schaefer ◽  
Olaf Pinkenburg ◽  
Tim D. Plant
Keyword(s):  
Phospholipase C ◽  
Transient Receptor Potential ◽  
Single Channel ◽  
Receptor Potential ◽  
High Sensitivity ◽  
Transient Receptor Potential Channel ◽  
Extracellular Ph ◽  
Dependent Manner ◽  
Open Probability ◽  
Transient Receptor

Mammalian members of the classical transient receptor potential channel subfamily (TRPC) are Ca2+-permeable cation channels involved in receptor-mediated increases in intracellular Ca2+. TRPC4 and TRPC5 form a group within the TRPC subfamily and are activated in a phospholipase C-dependent manner by an unidentified messenger. Unlike most other Ca2+-permeable channels, TRPC4 and -5 are potentiated by micromolar concentrations of La3+ and Gd3+. This effect results from an action of the cations at two glutamate residues accessible from the extracellular solution. Here, we show that TRPC4 and -5 respond to changes in extracellular pH. Lowering the pH increased both G protein-activated and spontaneous TRPC5 currents. Both effects were already observed with small reductions in pH (from 7.4 to 7.0) and increased up to pH 6.5. TRPC4 was also potentiated by decreases in pH, whereas TRPC6 was only inhibited, with a pIC50 of 5.7. Mutation of the glutamate residues responsible for lanthanoid sensitivity of TRPC5 (E543Q and E595Q) modified the potentiation of TRPC5 by acid. Further evidence for a similarity in the actions of lanthanoids and H+ on TRPC5 is the reduction in single channel conductance and dramatic increase in channel open probability in the presence of either H+ or Gd3+ that leads to larger integral currents. In conclusion, the high sensitivity of TRPC5 to H+ indicates that, in addition to regulation by phospholipase C and other factors, the channel may act as a sensor of pH that links decreases in extracellular pH to Ca2+ entry and depolarization.

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