Early-life persistent vitamin D deficiency-induced cardiovascular dysfunction in mice is mediated by transient receptor potential C channels

2021 ◽  
Vol 206 ◽  
pp. 105804
Author(s):  
Kimberly Stratford ◽  
Najwa Haykal-Coates ◽  
Leslie Thompson ◽  
Aimen Farraj ◽  
Mehdi Hazari
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Early Life ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cardiovascular Dysfunction ◽  
Transient Receptor

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.

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.

scholarly journals Blockade or deletion of transient receptor potential vanilloid 4 (TRPV4) is not protective in a murine model of sepsis

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 93 ◽  
Author(s):  
Claire A. Sand ◽  
Anna Starr ◽  
Manasi Nandi ◽  
Andrew D. Grant
Keyword(s):  
Blood Flow ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Laser Speckle ◽  
Microvascular Blood Flow ◽  
Transient Receptor Potential Vanilloid ◽  
Cardiovascular Dysfunction ◽  
Mesenteric Blood Flow ◽  
Significant Difference ◽  
Transient Receptor

Sepsis is a systemic inflammatory response triggered by microbial infection that can cause cardiovascular collapse, insufficient tissue perfusion and multi-organ failure. The cation channel transient receptor potential vanilloid 4 (TRPV4) is expressed in vascular endothelium and causes vasodilatation, but excessive TRPV4 activation leads to profound hypotension and circulatory collapse - key features of sepsis pathogenesis. We hypothesised that loss of TRPV4 signaling would protect against cardiovascular dysfunction in a mouse model of sepsis (endotoxaemia).Multi-parameter monitoring of conscious systemic haemodynamics (by radiotelemetry probe), mesenteric microvascular blood flow (laser speckle contrast imaging) and blood biochemistry (iSTAT blood gas analysis) was carried out in wild type (WT) and TRPV4 knockout (KO) mice. Endotoxaemia was induced by a single intravenous injection of lipopolysaccharide (LPS; 12.5 mg/kg) and systemic haemodynamics monitored for 24 h. Blood flow recording was then conducted under terminal anaesthesia after which blood was obtained for haematological/biochemical analysis. No significant differences were observed in baseline haemodynamics or mesenteric blood flow. Naïve TRPV4 KO mice were significantly acidotic relative to WT counterparts. Following induction of sepsis, all mice became significantly hypotensive, though there was no significant difference in the degree of hypotension between TRPV4 WT and KO mice. TRPV4 KO mice exhibited a higher sepsis severity score. While septic WT mice became significantly hypernatraemic relative to the naïve state, this was not observed in septic KO mice. Mesenteric blood flow was inhibited by topical application of the TRPV4 agonist GSK1016790A in naïve WT mice, but enhanced 24 h following LPS injection. Contrary to the initial hypothesis, loss of TRPV4 signaling (either through gene deletion or pharmacological antagonism) did not attenuate sepsis-induced cardiovascular dysfunction: in fact, pathology appeared to be modestly exaggerated in mice lacking TRPV4. Local targeting of TRPV4 signalling may be more beneficial than global inhibition in sepsis treatment.

Inositol lipids and TRPC channel activation

2007 ◽  
Vol 74 ◽  
pp. 37-45 ◽  
Author(s):  
James W. Putney
Keyword(s):  
Plasma Membrane ◽  
Phospholipase C ◽  
Transient Receptor Potential ◽  
Calcium Signalling ◽  
Receptor Potential ◽  
Breakdown Product ◽  
Channel Activation ◽  
Inositol Lipids ◽  
Transient Receptor ◽  
Secondary Mechanism

The original hypothesis put forth by Bob Michell in his seminal 1975 review held that inositol lipid breakdown was involved in the activation of plasma membrane calcium channels or ‘gates’. Subsequently, it was demonstrated that while the interposition of inositol lipid breakdown upstream of calcium signalling was correct, it was predominantly the release of Ca2+ that was activated, through the formation of Ins(1,4,5)P3. Ca2+ entry across the plasma membrane involved a secondary mechanism signalled in an unknown manner by depletion of intracellular Ca2+ stores. In recent years, however, additional non-store-operated mechanisms for Ca2+ entry have emerged. In many instances, these pathways involve homologues of the Drosophila trp (transient receptor potential) gene. In mammalian systems there are seven members of the TRP superfamily, designated TRPC1–TRPC7, which appear to be reasonably close structural and functional homologues of Drosophila TRP. Although these channels can sometimes function as store-operated channels, in the majority of instances they function as channels more directly linked to phospholipase C activity. Three members of this family, TRPC3, 6 and 7, are activated by the phosphoinositide breakdown product, diacylglycerol. Two others, TRPC4 and 5, are also activated as a consequence of phospholipase C activity, although the precise substrate or product molecules involved are still unclear. Thus the TRPCs represent a family of ion channels that are directly activated by inositol lipid breakdown, confirming Bob Michell's original prediction 30 years ago.

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