Sphingosine‐1‐phosphate phosphohydrolase 1 functionally antagonizes the microvascular effects of sphingosine kinase 1 and its metabolite sphingosine‐1‐phosphate
Bibliographic record
Abstract
S1P‐phosphohydrolase 1 (SPP1) putatively antagonizes the prominent effects of sphingosine kinase 1 (Sk1) / sphingosine‐1‐phosphate (S1P) signalling on microvascular tone. SPP1 mRNA is highly expressed in hamster resistance arteries, and tagged SPP1 protein resides in the cytosol and at the plasma membrane. Overexpression of SPP1 reduced resting tone, Ca 2+ sensitivity and myogenic vasoconstriction. Accordingly, treatment with antisense oligonucleotides yielded the opposite results. The co‐expression of SPP1 with Sk1 eliminated the previously reported Sk1‐mediated enhancements of tone and Ca 2+ sensitivity. Co‐expression of a phosphatase‐dead SPP1 mutant (SPP1 H208A ) failed to antagonize Sk1, excluding effects of protein overexpression that were unrelated to the S1P‐degrading function of SPP1. Treatment with antisense oligonucleotides or the specific inhibitor JTE013 identified (i) the S1P 2 receptor as the primary receptor mediating the effects of extracellular S1P, and (ii) the exogenous S1P concentration range where effects are entirely S1P 2 mediated. The latter was significantly altered by modulation of SPP1 expression, indicating that SPP1 accesses extracellular S1P pools. We conclude that SPP1 is the primary functional antagonist of Sk1 in the smooth muscle cells of resistance arteries, and consequently possesses potential clinical relevance in the control of tissue perfusion and systemic blood pressure.
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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 | 0.001 |
| 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".