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 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".