Up<sub>4</sub>A stimulates endothelium-independent contraction of isolated rat pulmonary artery
Bibliographic record
Abstract
Extracellular nucleotides, such as ATP, UDP, and UTP, regulate pulmonary vascular tone through P2X and P2Y receptors. Recently, uridine adenosine tetraphosphate (Up(4)A) was reported as a novel endothelium-derived vasoconstrictive factor. Up(4)A contains both purine and pyrimidine moieties, which potentially activate P2X and P2Y receptors. The present study examined the effect of Up(4)A on contractility of isolated rat pulmonary artery. Up(4)A at 1-100 microM stimulated contraction in a concentration-dependent manner. Up(4)A was equipotent as UTP and UDP in the endothelium-denuded artery while much more effective than UTP and UDP in endothelium-intact preparations. The vasoconstrictor effect of Up(4)A was inhibited by suramin but not IP(5)I or desensitization of P2X receptors with alpha,beta-methylene-ATP (alpha,beta-Me-ATP). Up(4)A-induced contraction was also inhibited by pretreatment with thapsigargin, nitrendipine, or EGTA but unaffected by H1152. Furthermore, unlike ATP and UTP, Up(4)A did not induce relaxation of endothelium-intact preparations precontracted with phenylephrine. These results suggest that Up(4)A is a potent vasoconstrictor, but not a vasodilator, of the rat pulmonary artery. Up(4)A likely acts through a suramin-sensitive P2Y receptor. The contractile effect of Up(4)A involves the entry of extracellular Ca(2+) and release of Ca(2+) from intracellular stores but not Ca(2+) sensitization via the RhoA/Rho kinase pathway. Up(4)A, therefore, potentially plays an important role in the regulation of pulmonary vascular tone.
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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) | 0.003 | 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".