Concerted action of associated proteins in the regulation of TRPV5 and TRPV6

2007 ◽  
Vol 35 (1) ◽  
pp. 115-119 ◽  
Author(s):  
J.P.H. Schoeber ◽  
J.G.J. Hoenderop ◽  
R.J.M. Bindels
Keyword(s):  
Hormonal Regulation ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
The Body ◽  
Transient Receptor Potential Vanilloid ◽  
Concerted Action ◽  
Associated Proteins ◽  
Calbindin D28k ◽  
Transient Receptor ◽  
Ca2 Channels

Ca2+ is an essential ion in all organisms and many physiological functions in the body rely on the exact maintenance of the Ca2+ balance. The epithelial Ca2+ channels TRPV5 [TRP (transient receptor potential) vanilloid 5] and TRPV6 are the most Ca2+-selective members of the TRP superfamily and are generally considered as the gatekeepers of Ca2+ entry across epithelia. TRPV5 is involved in Ca2+ reabsorption from pro-urine, while TRPV6 has an essential role in intestinal Ca2+ uptake. These channels are the prime targets of calciotropic hormonal regulation, including vitamin D and parathyroid hormone. In addition, extra- and intra-cellular signalling by associated proteins and Ca2+ itself play key roles in TRPV5 and TRPV6 regulation. In this paper, we describe the present understanding of the concerted action of calbindin-D28k, klotho and BSPRY (B-box and SPRY-domain-containing protein) at different levels throughout the epithelial cell to control Ca2+ influx at the luminal entry gate.

scholarly journals The Basal Pharmacology of Palmitoylethanolamide

2020 ◽  
Vol 21 (21) ◽  
pp. 7942 ◽  
Author(s):  
Linda Rankin ◽  
Christopher J. Fowler
Keyword(s):  
Transient Receptor Potential ◽  
Biological Effects ◽  
Receptor Potential ◽  
The Body ◽  
Transient Receptor Potential Vanilloid ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pharmacokinetic Properties ◽  
Endogenous Compound ◽  
Transient Receptor

Palmitoylethanolamide (PEA, N-hexadecanoylethanolamide) is an endogenous compound belonging to the family of N-acylethanolamines. PEA has anti-inflammatory and analgesic properties and is very well tolerated in humans. In the present article, the basal pharmacology of PEA is reviewed. In terms of its pharmacokinetic properties, most work has been undertaken upon designing formulations for its absorption and upon characterising the enzymes involved in its metabolism, but little is known about its bioavailability, tissue distribution, and excretion pathways. PEA exerts most of its biological effects in the body secondary to the activation of peroxisome proliferator-activated receptor-α (PPAR-α), but PPAR-α-independent pathways involving other receptors (Transient Receptor Potential Vanilloid 1 (TRPV1), GPR55) have also been identified. Given the potential clinical utility of PEA, not least for the treatment of pain where there is a clear need for new well-tolerated drugs, we conclude that the gaps in our knowledge, in particular those relating to the pharmacokinetic properties of the compound, need to be filled.

scholarly journals Role of TRPV4 in the Diagnosis and Treatment of Helicobacter pylori Infection in Children with Duodenal Ulcers

2022 ◽  
Vol 2022 ◽  
pp. 1-7
Author(s):  
Chuanying Li ◽  
Rong Cheng ◽  
Lin Li ◽  
Miaomiao Chen ◽  
Cheng Wu
Keyword(s):  
Duodenal Ulcer ◽  
Transient Receptor Potential ◽  
Animal Experiments ◽  
Receptor Potential ◽  
Diagnostic Value ◽  
The Body ◽  
Inflammatory Factors ◽  
Transient Receptor Potential Vanilloid ◽  
Duodenal Ulcers ◽  
Transient Receptor

Duodenal ulcer seriously affects the quality of life and life safety of children, but the pathogenesis of children with duodenal ulcer is still unclear. As an important second messenger in the body, Ca2+ participates in the physiological and pathological processes of various diseases. Therefore, transient receptor potential vanilloid type 4 (TRPV4) as one of the channels that mediate Ca2+ has attracted widespread attention in recent years. Here, we found that TRPV4 is highly expressed in children with duodenal ulcer and has good diagnostic value through specimens of children with duodenal ulcer, and animal experiments have proved that TRPV4 is also highly expressed in duodenal ulcer mice. In addition, TRPV4 can enhance intestinal permeability, thereby promoting further infiltration of inflammatory factors. In summary, these results indicate that TRPV4 is involved in the occurrence and development of duodenal ulcer. Therefore, this study provides the diagnostic and therapeutic value of TRPV4 in children with duodenal ulcer.

scholarly journals The role of calbindin-D28k on renal calcium and magnesium handling during treatment with loop and thiazide diuretics

2016 ◽  
Vol 310 (3) ◽  
pp. F230-F236 ◽  
Author(s):  
Chien-Te Lee ◽  
Hwee-Yeong Ng ◽  
Yueh-Ting Lee ◽  
Li-Wen Lai ◽  
Yeong-Hau H. Lien
Keyword(s):  
Gene Expression ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Thiazide Diuretics ◽  
Ca Transport ◽  
Calbindin D28k ◽  
Transient Receptor ◽  
Transport Molecules

Calbindin-D28k (CBD-28k) is a calcium binding protein located in the distal convoluted tubule (DCT) and plays an important role in active calcium transport in the kidney. Loop and thiazide diuretics affect renal Ca and Mg handling: both cause Mg wasting, but have opposite effects on Ca excretion as loop diuretics increase, but thiazides decrease, Ca excretion. To understand the role of CBD-28k in renal Ca and Mg handling in response to diuretics treatment, we investigated renal Ca and Mg excretion and gene expression of DCT Ca and Mg transport molecules in wild-type (WT) and CBD-28k knockout (KO) mice. Mice were treated with chlorothiazide (CTZ; 50 mg·kg−1·day−1) or furosemide (FSM; 30 mg·kg−1·day−1) for 3 days. To avoid volume depletion, salt was supplemented in the drinking water. Urine Ca excretion was reduced in WT, but not in KO mice, by CTZ. FSM induced similar hypercalciuria in both groups. DCT Ca transport molecules, including transient receptor potential vanilloid 5 (TRPV5), TRPV6, and CBD-9k, were upregulated by CTZ and FSM in WT, but not in KO mice. Urine Mg excretion was increased and transient receptor potential subfamily M, member 6 (TRPM6) was upregulated by both CTZ and FSM in WT and KO mice. In conclusion, CBD-28k plays an important role in gene expression of DCT Ca, but not Mg, transport molecules, which may be related to its being a Ca, but not a Mg, intracellular sensor. The lack of upregulation of DCT Ca transport molecules by thiazides in the KO mice indicates that the DCT Ca transport system is critical for Ca conservation by thiazides.

scholarly journals TRPV4: Molecular Conductor of a Diverse Orchestra

2016 ◽  
Vol 96 (3) ◽  
pp. 911-973 ◽  
Author(s):  
John P. M. White ◽  
Mario Cibelli ◽  
Laszlo Urban ◽  
Bernd Nilius ◽  
J. Graham McGeown ◽  
...  
Keyword(s):  
Ion Channel ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
The Body ◽  
Transient Receptor Potential Vanilloid ◽  
Ionotropic Receptor ◽  
Disease States ◽  
Health And Disease ◽  
Transient Receptor ◽  
And Function

Transient receptor potential vanilloid type 4 (TRPV4) is a calcium-permeable nonselective cation channel, originally described in 2000 by research teams led by Schultz ( Nat Cell Biol 2: 695 –702, 2000) and Liedtke ( Cell 103: 525–535, 2000). TRPV4 is now recognized as being a polymodal ionotropic receptor that is activated by a disparate array of stimuli, ranging from hypotonicity to heat and acidic pH. Importantly, this ion channel is constitutively expressed and capable of spontaneous activity in the absence of agonist stimulation, which suggests that it serves important physiological functions, as does its widespread dissemination throughout the body and its capacity to interact with other proteins. Not surprisingly, therefore, it has emerged more recently that TRPV4 fulfills a great number of important physiological roles and that various disease states are attributable to the absence, or abnormal functioning, of this ion channel. Here, we review the known characteristics of this ion channel's structure, localization and function, including its activators, and examine its functional importance in health and disease.

Repeated capsaicin patch applications in patients with localized peripheral neuropathic pain

Ból ◽  
2021 ◽  
Vol 22 (1) ◽  
pp. 56-65
Author(s):  
Małgorzata Malec-Milewska ◽  
Jerzy Wordliczek ◽  
Renata Zajączkowska
Keyword(s):  
Neuropathic Pain ◽  
Transient Receptor Potential ◽  
Significant Proportion ◽  
Case Series ◽  
Receptor Potential ◽  
The Body ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor ◽  
Good Treatment Option ◽  
Localized Neuropathic Pain

Neuropathic pain is still a challenging problem. It is experienced by millions of people worldwide, with an approximate prevalence of 7‒10% in the general population. Despite the availability of a variety of treatment methods, a significant proportion of patients suffer from poorly controlled neuropathic pain. Capsaicin is a highly selective TRPV1 (Transient Receptor Potential Vanilloid Type 1) agonist. When applied topically, it leads to the defunctionalisation of hyperactive nociceptive receptors, temporary destruction of peripheral nerve endings, and a significant reduction or cessation of pain. Therefore 8% capsaicin patches are used to treat several peripheral, localized neuropathic pain syndromes. The study aimed to present a case series of patients suffering from peripheral, localized neuropathic pain in case the use of repeated applications of 8% capsaicin patches significantly reduced the intensity of pain. In 5 out of 6 patients we observed a gradual extension of the pain relief period until the pain disappeared, which led to the reduction or discontinuation of systemic pharmacotherapy. In summary, a therapy limited to a certain area of the body, without potential systemic adverse effects, which requires repetition at fairly long intervals, appears to be a good treatment option.

scholarly journals Expression of Transient Receptor Potential Ankyrin 1 and Transient Receptor Potential Vanilloid 1 in the Gut of the Peri-Weaning Pig Is Strongly Dependent on Age and Intestinal Site

Animals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2417
Author(s):  
Elout Van Liefferinge ◽  
Noémie Van Noten ◽  
Jeroen Degroote ◽  
Gunther Vrolix ◽  
Mario Van Poucke ◽  
...  
Keyword(s):  
Small Intestine ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
The Body ◽  
Enteroendocrine Cells ◽  
Sensory Transduction ◽  
Transient Receptor Potential Vanilloid ◽  
Distal Small Intestine ◽  
Transient Receptor

Transient receptor potential (TRP) channels contribute to sensory transduction in the body, agonized by a variety of stimuli, such as phytochemicals, and they are predominantly distributed in afferent neurons. Evidence indicates their expression in non-neuronal cells, demonstrating their ability to modulate gastrointestinal function. Targeting TRP channels could potentially be used to regulate gastrointestinal secretion and motility, yet their expression in the pig is unknown. This study investigated TRPA1 and TRPV1 expression in different gut locations of piglets of varying age. Colocalization with enteroendocrine cells was established by immunohistochemistry. Both channels were expressed in the gut mucosa. TRPV1 mRNA abundance increased gradually in the stomach and small intestine with age, most notably in the distal small intestine. In contrast, TRPA1 exhibited sustained expression across ages and locations, with the exception of higher expression in the pylorus at weaning. Immunohistochemistry confirmed the endocrine nature of both channels, showing the highest frequency of colocalization in enteroendocrine cells for TRPA1. Specific co-localization on GLP-1 immunoreactive cells indicated their possible role in GLP-1 release and the concomitant intestinal feedback mechanism. Our results indicate that TRPA1 and TRPV1 could play a role in gut enteroendocrine activity. Moreover, age and location in the gut significantly affected gene expression.

scholarly journals Changes in TRPV1-Mediated Physiological Function in Rats Systemically Treated With Capsaicin on the Neonate

2020 ◽  
Vol 21 (9) ◽  
pp. 3143 ◽  
Author(s):  
Keun-Yeong Jeong
Keyword(s):  
Body Temperature ◽  
Pain Perception ◽  
Transient Receptor Potential ◽  
Core Body Temperature ◽  
Receptor Potential ◽  
The Body ◽  
Transient Receptor Potential Vanilloid ◽  
Temperature Rhythm ◽  
Transient Receptor ◽  
Body Temperature Increase

Capsaicin is the active component of chili peppers and is a hydrophobic, colorless, odorless, and crystalline to waxy compound. The transient receptor potential vanilloid 1 (TRPV1) is the capsaicin receptor channels that are involved in a variety of functions like transduction and transmission of the physiological stimulus. Subcutaneous injection of capsaicin to a newborn rat leads to involuntary lifelong TRPV1 desensitization. Various physiological changes including sensory and homeostatic actions in the body associated with neonatal capsaicin treatment are induced by direct TRPV1 channel targeting. Interesting changes include unique phenomena such as the reduction in pain perception, abnormal body temperature, increase in infection, infectious or neuropathological itching, and irregular circadian core body temperature rhythm. These symptoms are associated with relatively higher fever or loss of sensory c-fiber related to TRPV1 desensitization. The aforementioned outcomes not only provide a warning about the risk of capsaicin exposure in newborns but also indicate the possible occurrence of relatively rare diseases that are difficult to diagnose. Therefore, Therefore, the present review aims to summarize the unique phenomena caused by systemic capsaicin administration in neonatal rats.

scholarly journals Migraine-relevant sex-dependent activation of mouse meningeal afferents by TRPM3 agonists

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
G. Krivoshein ◽  
E. A. Tolner ◽  
van den Maagdenberg AMJM ◽  
R. A. Giniatullin
Keyword(s):  
Sex Difference ◽  
Hormonal Regulation ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Male And Female ◽  
Female Mice ◽  
Trpv1 Channels ◽  
Migraine Pain ◽  
Transient Receptor

Abstract Background Migraine is a common brain disorder that predominantly affects women. Migraine pain seems mediated by the activation of mechanosensitive channels in meningeal afferents. Given the role of transient receptor potential melastatin 3 (TRPM3) channels in mechanical activation, as well as hormonal regulation, these channels may play a role in the sex difference in migraine. Therefore, we investigated whether nociceptive firing induced by TRPM3 channel agonists in meningeal afferents was different between male and female mice. In addition, we assessed the relative contribution of mechanosensitive TRPM3 channels and that of mechanosensitive Piezo1 channels and transient receptor potential vanilloid 1 (TRPV1) channels to nociceptive firing relevant to migraine in both sexes. Methods Ten- to 13-week-old male and female wildtype (WT) C57BL/6 J mice were used. Nociceptive spikes were recorded directly from nerve terminals in the meninges in the hemiskull preparations. Results Selective agonists of TRPM3 channels profoundly activated peripheral trigeminal nerve fibres in mouse meninges. A sex difference was observed for nociceptive firing induced by either PregS or CIM0216, both agonists of TRPM3 channels, with the induced firing being particularly prominent for female mice. Application of Yoda1, an agonist of Piezo1 channels, or capsaicin activating TRPV1 channels, although also leading to increased nociceptive firing of meningeal fibres, did not reveal a sex difference. Cluster analyses of spike activities indicated a massive and long-lasting activation of TRPM3 channels with preferential induction of large-amplitude spikes in female mice. Additional spectral analysis revealed ​a dominant contribution of spiking activity in the α- and β-ranges following TRPM3 agonists in female mice. Conclusions Together, we revealed a specific mechanosensitive profile of nociceptive firing in females and suggest TRPM3 channels as a potential novel candidate for the generation of migraine pain, with particular relevance to females.

Segmental transport of Ca2+ and Mg2+ along the gastrointestinal tract

2015 ◽  
Vol 308 (3) ◽  
pp. G206-G216 ◽  
Author(s):  
Anke L. Lameris ◽  
Pasi I. Nevalainen ◽  
Daphne Reijnen ◽  
Ellen Simons ◽  
Jelle Eygensteyn ◽  
...  
Keyword(s):  
Vitamin D ◽  
Gastrointestinal Tract ◽  
Intestinal Absorption ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
The Body ◽  
Time Dependent ◽  
Transient Receptor Potential Vanilloid ◽  
Dependent Manner ◽  
Transient Receptor

Calcium (Ca2+) and magnesium (Mg2+) ions are involved in many vital physiological functions. Since dietary intake is the only source of minerals for the body, intestinal absorption is essential for normal homeostatic levels. The aim of this study was to characterize the absorption of Ca2+ as well as Mg2+ along the gastrointestinal tract at a molecular and functional level. In both humans and mice the Ca2+ channel transient receptor potential vanilloid subtype 6 (TRPV6) is expressed in the proximal intestinal segments, whereas Mg2+ channel transient receptor potential melastatin subtype 6 (TRPM6) is expressed in the distal parts of the intestine. A method was established to measure the rate of Mg2+ absorption from the intestine in a time-dependent manner by use of 25Mg2+. In addition, local absorption of Ca2+ and Mg2+ in different segments of the intestine of mice was determined by using surgically implanted intestinal cannulas. By these methods, it was demonstrated that intestinal absorption of Mg2+ is regulated by dietary needs in a vitamin D-independent manner. Also, it was shown that at low luminal concentrations, favoring transcellular absorption, Ca2+ transport mainly takes place in the proximal segments of the intestine, whereas Mg2+ absorption predominantly occurs in the distal part of the gastrointestinal tract. Vitamin D treatment of mice increased serum Mg2+ levels and 24-h urinary Mg2+ excretion, but not intestinal absorption of 25Mg2+. Segmental cannulation of the intestine and time-dependent absorption studies using 25Mg2+ provide new ways to study intestinal Mg2+ absorption.

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