Biphenyl 2,3′,4,5′,6‐pentakisphosphate, a novel inositol polyphosphate surrogate, modulates Ca <sup>2+</sup> responses in rat hepatocytes
Bibliographic record
Abstract
ABSTRACT Benzene polyphosphates containing phosphate groups on one ring are Ins(1,4,5)P 3 5‐phosphatase inhibitors when evaluated against type‐I Ins(1,4,5)P 3 5‐phosphatase. A novel biphenyl derivative, biphenyl 2,3′,4,5′,6‐pentakisphosphate, with five phosphate groups on two rings was synthesized: It inhibited the activity of two inositol 5‐phosphatases: type I and SHIP2 with Ins(1,3,4,5)P 4 as substrate. The inhibition was competitive with respect to the substrate. IC 50 value measured in rat hepatocytes, which contains the native Ins(1,4,5)P 3 5‐phosphatase, was in the micromolar range at 1.0 μM Ins(1,4,5)P 3 as substrate. Biphenyl 2,3′,4,5′,6‐pentakisphosphate did not affect the activity of Ins(1,4,5)P 3 3‐kinase A in the 5‐100 μM range. Surprisingly, experimental evidence supports an effect of biphenyl 2,3′,4,5′,6‐pentakisphosphate at the level of the Ins(1,4,5)P 3 receptor. Finally, when injected into rat hepatocytes, the analog affected the frequency of Ca 2+ oscillations in a positive or negative way depending on its concentration. At very high concentrations of the analog, Ca 2+ oscillations were even suppressed. These data were interpreted as a dual effect of the biphenyl 2,3′,4,5′,6‐pentakisphosphate on cytosolic [Ca 2+ ] increases: an activation effect through an increase in Ins(1,4,5)P 3 level via Ins(1,4,5)P 3 5‐phosphatase inhibition and an inhibitory effect, which was exerted directly on the Ins(1,4,5)P 3 receptor. Thus, our data show for the first time that the frequency of Ca 2+ oscillations in response to a Ca 2+ ‐mobilizing agonist can be controlled by inhibitors of type‐I Ins(1,4,5)P 3 5‐phosphatase.—Vandeput, F., Combettes, L., Mills, S. J., Backers, K., Wohlkönig, A., Parys, J. B., De Smedt, H., Missiaen, L., Dupont, G., Potter, B. V. L., Erneux, C. Biphenyl 2,3′,4,5′,6‐pentakisphosphate, a novel inositol polyphosphate surrogate, modulates Ca2+ responses in rat hepatocytes. FASEB J. 21, 1481–1491 (2007)
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".