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

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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The Basal Pharmacology of Palmitoylethanolamide

International Journal of Molecular Sciences ◽

10.3390/ijms21217942 ◽

2020 ◽

Vol 21 (21) ◽

pp. 7942 ◽

Cited By ~ 2

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.

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The nonselective cation channel TRPV4 inhibits angiotensin II receptors

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.014325 ◽

2020 ◽

Vol 295 (29) ◽

pp. 9986-9997

Author(s):

Nicholas W. Zaccor ◽

Charlotte J. Sumner ◽

Solomon H. Snyder

Keyword(s):

Angiotensin Ii ◽

G Protein ◽

Transient Receptor Potential ◽

Trp Channels ◽

Receptor Potential ◽

Trp Channel ◽

Luciferase Assay ◽

Transient Receptor Potential Vanilloid ◽

Dependent Manner ◽

Transient Receptor

G-protein–coupled receptors (GPCRs) are a ubiquitously expressed family of receptor proteins that regulate many physiological functions and other proteins. They act through two dissociable signaling pathways: the exchange of GDP to GTP by linked G-proteins and the recruitment of β-arrestins. GPCRs modulate several members of the transient receptor potential (TRP) channel family of nonselective cation channels. How TRP channels reciprocally regulate GPCR signaling is less well-explored. Here, using an array of biochemical approaches, including immunoprecipitation and fluorescence, calcium imaging, phosphate radiolabeling, and a β-arrestin–dependent luciferase assay, we characterize a GPCR–TRP channel pair, angiotensin II receptor type 1 (AT1R), and transient receptor potential vanilloid 4 (TRPV4), in primary murine choroid plexus epithelial cells and immortalized cell lines. We found that AT1R and TRPV4 are binding partners and that activation of AT1R by angiotensin II (ANGII) elicits β-arrestin–dependent inhibition and internalization of TRPV4. Activating TRPV4 with endogenous and synthetic agonists inhibited angiotensin II–mediated G-protein–associated second messenger accumulation, AT1R receptor phosphorylation, and β-arrestin recruitment. We also noted that TRPV4 inhibits AT1R phosphorylation by activating the calcium-activated phosphatase calcineurin in a Ca2+/calmodulin–dependent manner, preventing β-arrestin recruitment and receptor internalization. These findings suggest that when TRP channels and GPCRs are co-expressed in the same tissues, many of these channels can inhibit GPCR desensitization.

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

Biochemical Society Transactions ◽

10.1042/bst0350115 ◽

2007 ◽

Vol 35 (1) ◽

pp. 115-119 ◽

Cited By ~ 32

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.

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Evidence for a Role of Prolactin in Calcium Homeostasis: Regulation of Intestinal Transient Receptor Potential Vanilloid Type 6, Intestinal Calcium Absorption, and the 25-Hydroxyvitamin D3 1α Hydroxylase Gene by Prolactin

Endocrinology ◽

10.1210/en.2010-0033 ◽

2010 ◽

Vol 151 (7) ◽

pp. 2974-2984 ◽

Cited By ~ 61

Author(s):

Dare V. Ajibade ◽

Puneet Dhawan ◽

Adam J. Fechner ◽

Mark B. Meyer ◽

J. Wesley Pike ◽

...

Keyword(s):

Vitamin D ◽

Calcium Homeostasis ◽

Calcium Transport ◽

Transient Receptor Potential ◽

Prolactin Receptor ◽

Receptor Potential ◽

Transient Receptor Potential Vanilloid ◽

Calbindin D9k ◽

Intestinal Calcium Transport ◽

Transient Receptor

Increased calcium transport has been observed in vitamin D-deficient pregnant and lactating rats, indicating that another factor besides 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is involved in intestinal calcium transport. To investigate prolactin as a hormone involved in calcium homeostasis, vitamin D-deficient male mice were injected with 1,25(OH)2D3, prolactin, or prolactin + 1,25(OH)2D3. Prolactin alone (1 μg/g body weight 48, 24, and 4 h before termination) significantly induced duodenal transient receptor potential vanilloid type 6 (TRPV6) mRNA (4-fold) but caused no change in calbindin-D9k. Combined treatment with 1,25(OH)2D3 and prolactin resulted in an enhancement of the 1,25(OH)2D3 induction of duodenal TRPV6 mRNA, calbindin-D9k mRNA, and an induction of duodenal calcium transport [P < 0.05 compared with 1,25(OH)2D3 alone]. Because lactation is associated with an increase in circulating 1,25(OH)2D3, experiments were done to determine whether prolactin also has a direct effect on induction of 25-hydroxyvitamin D3 1α hydroxylase [1α(OH)ase]. Using AOK B-50 cells cotransfected with the prolactin receptor and the mouse 1α(OH)ase promoter −1651/+22 cooperative effects between prolactin and signal transducer and activator of transcription 5 were observed in the regulation of 1α(OH)ase. In addition, in prolactin receptor transfected AOK B-50 cells, prolactin treatment (400 ng/ml) and signal transducer and activator of transcription 5 significantly induced 1α(OH)ase protein as determined by Western blot analysis. Thus, prolactin, by multiple mechanisms, including regulation of vitamin D metabolism, induction of TRPV6 mRNA, and cooperation with 1,25(OH)2D3 in induction of intestinal calcium transport genes and intestinal calcium transport, can act as an important modulator of vitamin D-regulated calcium homeostasis.

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

BioMed Research International ◽

10.1155/2022/2777882 ◽

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.

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Structural insight into TRPV5 channel function and modulation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1820323116 ◽

2019 ◽

Vol 116 (18) ◽

pp. 8869-8878 ◽

Cited By ~ 26

Author(s):

Shangyu Dang ◽

Mark K. van Goor ◽

Daniel Asarnow ◽

YongQiang Wang ◽

David Julius ◽

...

Keyword(s):

Transient Receptor Potential ◽

Receptor Potential ◽

Transient Receptor Potential Vanilloid ◽

Dependent Manner ◽

Calcium Dependent ◽

Resolution Electron ◽

Trpv Channels ◽

Transient Receptor ◽

Lipid Nanodiscs ◽

Insight Into

TRPV5 (transient receptor potential vanilloid 5) is a unique calcium-selective TRP channel essential for calcium homeostasis. Unlike other TRPV channels, TRPV5 and its close homolog, TRPV6, do not exhibit thermosensitivity or ligand-dependent activation but are constitutively open at physiological membrane potentials and modulated by calmodulin (CaM) in a calcium-dependent manner. Here we report high-resolution electron cryomicroscopy structures of truncated and full-length TRPV5 in lipid nanodiscs, as well as of a TRPV5 W583A mutant and TRPV5 in complex with CaM. These structures highlight the mechanism of calcium regulation and reveal a flexible stoichiometry of CaM binding to TRPV5.

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Vitamin D is an endogenous partial agonist of the transient receptor potential vanilloid 1 channel

The Journal of Physiology ◽

10.1113/jp279961 ◽

2020 ◽

Vol 598 (19) ◽

pp. 4321-4338 ◽

Cited By ~ 1

Author(s):

Wentong Long ◽

Mohammad Fatehi ◽

Shubham Soni ◽

Rashmi Panigrahi ◽

Koenraad Philippaert ◽

...

Keyword(s):

Vitamin D ◽

Transient Receptor Potential ◽

Partial Agonist ◽

Receptor Potential ◽

Transient Receptor Potential Vanilloid ◽

Transient Receptor

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Abstract 326: TRPV2 Regulates Cardiomyocyte Function via Altering Ca 2+ Cycling

Circulation Research ◽

10.1161/res.111.suppl_1.a326 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Xiaoqian Gao ◽

Sheryl Koch ◽

Min Jiang ◽

Nathan Robbins ◽

Wenfeng Cai ◽

...

Keyword(s):

Transient Receptor Potential ◽

Ventricular Myocytes ◽

Receptor Potential ◽

Ruthenium Red ◽

Transient Receptor Potential Vanilloid ◽

Dependent Manner ◽

Noxious Heat ◽

Cardiac Tissues ◽

Membrane Stretching ◽

Transient Receptor

TRPV2 is a member of transient receptor potential vanilloid (TRPV) family. As a Ca 2+ channel, it can detect various stimuli such as noxious heat (>52°C), membrane stretching, as well as a number of exogenous chemicals, including probenecid, 2-aminoethoxydiphenyl borate, and lysophospholipids. TRPV2 has been found in many tissue types, including neuron and kidney, but the function of TRPV2 in the heart is poorly understood. Here we show TRPV2 is involved in the Ca 2+ cycling process and then regulates the function of the cardiomyocyte. We identified the mRNA expression of TRPV2 in the cardiac tissues of mice using real-time PCR. By performing echocardiography we found that administration of probenecid, a selective TRPV2 agonist, increased cardiac ejection fraction in mice. This positive inotropic effect of probenecid was also shown in Langendorff perfused mice hearts as increased peak +dP/dt. In isolated ventricular myocytes, we found that probenecid significantly increased myocyte fractional shortening in a dose-dependent manner, which was fully blocked by ruthenium red, a non-selective TRPV2 blocker. We also performed fluorescent studies to examine myocyte Ca 2+ cycling. We found that probenecid significantly increased Ca 2+ transient and resting-state Ca 2+ sparks and this effect was eliminated by ruthenium red. When Ca 2+ storage in sarcoplasmic reticulum (SR) was depleted with caffeine, and SR Ca 2+ reuptake was blocked by thapsigargin at the same time, probenecid did not show any effects in either Ca 2+ transient or Ca 2+ sparks. Our patch clamp experiments indicate that probenecid treatment does not trigger any significant transmembrane Ca 2+ influx. These results point to the important role of TRPV2 in regulating SR Ca 2+ release. In conclusion, TRPV2 activation may contribute to increased SR Ca 2+ release, leading to the enhancement of myocyte contractility. Thus, TRPV2 plays a potentially important role in controlling the cellular function of heart.

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TRPV4 contributes to stretch-induced hypercontractility and time-dependent dysfunction in the aged heart

10.32469/10355/73833 ◽

2019 ◽

Author(s):

◽

Adam Bruce Veteto

Keyword(s):

Cardiovascular Disease ◽

Cardiac Function ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Time Dependent ◽

Calcium Handling ◽

Transient Receptor Potential Vanilloid ◽

University Of Missouri ◽

Transient Receptor ◽

The University

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Aims: Cardiovascular disease remains the greatest cause of mortality in Americans over 65. The stretch-activated Transient Receptor Potential Vanilloid-4 (TRPV4) ion channel is expressed in cardiomyocytes of the aged heart. This investigation tests the hypothesis that TRPV4 alters calcium handling and cardiac function in response to increased ventricular preload and cardiomyocyte stretch.

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