scholarly journals The Human Transient Receptor Potential Vanilloid Type 6 Distal Promoter Contains Multiple Vitamin D Receptor Binding Sites that Mediate Activation by 1,25-Dihydroxyvitamin D3 in Intestinal Cells

2006 ◽  
Vol 20 (6) ◽  
pp. 1447-1461 ◽  
Author(s):  
Mark B. Meyer ◽  
Makoto Watanuki ◽  
Sungtae Kim ◽  
Nirupama K. Shevde ◽  
J. Wesley Pike
Keyword(s):  
Vitamin D ◽  
Receptor Binding ◽  
Binding Sites ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Intestinal Cells ◽  
Transient Receptor Potential Vanilloid ◽  
Dihydroxyvitamin D3 ◽  
Transient Receptor ◽  
Distal Promoter

scholarly journals TRPV1: Structure, Endogenous Agonists, and Mechanisms

2020 ◽  
Vol 21 (10) ◽  
pp. 3421 ◽  
Author(s):  
Miguel Benítez-Angeles ◽  
Sara Luz Morales-Lázaro ◽  
Emmanuel Juárez-González ◽  
Tamara Rosenbaum
Keyword(s):  
Ion Channel ◽  
Binding Sites ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channel ◽  
Field Of Study ◽  
Transient Receptor ◽  
Shed Light ◽  
Made In

The Transient Receptor Potential Vanilloid 1 (TRPV1) channel is a polymodal protein with functions widely linked to the generation of pain. Several agonists of exogenous and endogenous nature have been described for this ion channel. Nonetheless, detailed mechanisms and description of binding sites have been resolved only for a few endogenous agonists. This review focuses on summarizing discoveries made in this particular field of study and highlighting the fact that studying the molecular details of activation of the channel by different agonists can shed light on biophysical traits that had not been previously demonstrated.

scholarly journals 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 ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 2974-2984 ◽  
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.

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

2020 ◽  
Vol 598 (19) ◽  
pp. 4321-4338 ◽  
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

scholarly journals Active Intestinal Calcium Transport in the Absence of Transient Receptor Potential Vanilloid Type 6 and Calbindin-D9k

Endocrinology ◽  
2008 ◽  
Vol 149 (6) ◽  
pp. 3196-3205 ◽  
Author(s):  
Bryan S. Benn ◽  
Dare Ajibade ◽  
Angela Porta ◽  
Puneet Dhawan ◽  
Matthias Hediger ◽  
...  
Keyword(s):  
Vitamin D ◽  
Calcium Transport ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Fold Increase ◽  
Transient Receptor Potential Vanilloid ◽  
Low Calcium Diet ◽  
Calbindin D9k ◽  
Intestinal Calcium Transport ◽  
Transient Receptor

To study the role of the epithelial calcium channel transient receptor potential vanilloid type 6 (TRPV6) and the calcium-binding protein calbindin-D9k in intestinal calcium absorption, TRPV6 knockout (KO), calbindin-D9k KO, and TRPV6/calbindin-D9k double-KO (DKO) mice were generated. TRPV6 KO, calbindin-D9k KO, and TRPV6/calbindin-D9k DKO mice have serum calcium levels similar to those of wild-type (WT) mice (∼10 mg Ca2+/dl). In the TRPV6 KO and the DKO mice, however, there is a 1.8-fold increase in serum PTH levels (P < 0.05 compared with WT). Active intestinal calcium transport was measured using the everted gut sac method. Under low dietary calcium conditions there was a 4.1-, 2.9-, and 3.9-fold increase in calcium transport in the duodenum of WT, TRPV6 KO, and calbindin-D9k KO mice, respectively (n = 8–22 per group; P > 0.1, WT vs. calbindin-D9k KO, and P < 0.05, WT vs. TRPV6 KO on the low-calcium diet). Duodenal calcium transport was increased 2.1-fold in the TRPV6/calbindin-D9k DKO mice fed the low-calcium diet (P < 0.05, WT vs. DKO). Active calcium transport was not stimulated by low dietary calcium in the ileum of the WT or KO mice. 1,25-Dihydroxyvitamin D3 administration to vitamin D-deficient null mutant and WT mice also resulted in a significant increase in duodenal calcium transport (1.4- to 2.0-fold, P < 0.05 compared with vitamin D-deficient mice). This study provides evidence for the first time using null mutant mice that significant active intestinal calcium transport occurs in the absence of TRPV6 and calbindin-D9k, thus challenging the dogma that TRPV6 and calbindin-D9k are essential for vitamin D-induced active intestinal calcium transport.

scholarly journals Phosphoinositides regulate the TRPV1 channel via two functionally distinct binding sites

2019 ◽  
Author(s):  
Aysenur Torun Yazici ◽  
Eleonora Gianti ◽  
Marina A. Kasimova ◽  
Vincenzo Carnevale ◽  
Tibor Rohacs
Keyword(s):  
Binding Site ◽  
Binding Sites ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channel ◽  
Distinct Site ◽  
Excised Patches ◽  
Transient Receptor ◽  
Dynamics Simulations

AbstractRegulation of the heat- and capsaicin-activated Transient Receptor Potential Vanilloid 1 (TRPV1) channel by phosphoinositides is controversial. In a recent cryoEM structure, an endogenous phosphoinositide was detected in the vanilloid binding site, and phosphoinositides were proposed to act as competitive vanilloid antagonists. This model is difficult to reconcile with phosphatidylinositol 4,5- bisphosphate [PtdIns(4,5)P2] being a well established positive regulator of TRPV1. To resolve this controversy, we propose that phosphoinositides regulate TRPV1 via two functionally distinct binding sites. Our molecular dynamics simulations show that phosphatidylinositol (PtdIns) is more stable in the vanilloid binding site, whereas a distinct site responsible for activation is preferentially occupied by PtdIns(4,5)P2. Consistently, we show that in the presence of PtdIns(4,5)P2 in excised patches PtdIns partially inhibited TRPV1 activity induced by low, but not high capsaicin concentrations. In the absence of PtdIns(4,5)P2 on the other hand, PtdIns partially stimulated TRPV1 activity presumably by binding to the activating site. Overall, our data resolve a major controversy in the regulation of TRPV1.

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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