Basolateral Calcium Sensing Receptor Mediated Regulation of TRPV6‐dependent Transcellular Calcium Absorption
Bibliographic record
Abstract
The plasma concentrations of ionized calcium (Ca 2+ ) is maintained within a narrow physiological range by amending the release of parathyroid hormone and through direct effects of the calcium sensing receptor (CaSR) on the renal tubule. Combined, these mechanisms alter intestinal Ca 2+ absorption via 1,25‐dihydroxy vitamin D 3 , bone resorption, and renal Ca 2+ excretion. The CaSR is also expressed in intestinal epithelium, but its function with respect to intestinal Ca 2+ absorption are unknown. In the present study, we describe a mechanism by which the intestine detects and regulates Ca 2+ absorption. Chronic CaSR activation decreased the expression of genes driving transcellular Ca 2+ absorption, with the greatest effect observed in the proximal colon. To directly assess Ca 2+ fluxes across the proximal colon, radioactive tracer experiments were performed ex vivo in Ussing chambers. Increased extracellular Ca 2+ or basolateral application of the calcimimetic cinacalcet decreased net Ca 2+ absorption acutely. Conversely, Ca 2+ absorption was increased when the extracellular buffer was switched to one containing a lower Ca 2+ concentration. These responses were absent in mice expressing a non‐functional TRPV6, TRPV6 D541A . Cinacalcet also attenuated Ca 2+ fluxes through TRPV6 in X enopus oocytes when co‐expressed with the CaSR. Moreover, the phospholipase C inhibitor, U73122, prevented cinacalcet‐mediated inhibition of Ca 2+ flux in both Xenopus ooctyes and murine proximal colon. Together, our results reveal a novel regulatory pathway whereby activation of the CaSR in the basolateral membrane of the proximal large bowel attenuates Ca 2+ absorption via genomic and non‐genomic regulation of TRPV6 to prevent hypercalcemia. Support or Funding Information This work was funded by the Canadian Institute of Health Research, the Natural Sciences and Engineering Research Council, and the Women and Children's Health Research Institute . This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".