Contraction to big endothelin‐1, big endothelin‐2 and big endothelin‐3, and endothelin‐converting enzyme inhibition in human isolated bronchi
Bibliographic record
Abstract
All three endothelin precursor peptides, i.e. big endothelin-1 (big ET-1), big endothelin-2 (big ET-2) and big endothelin-3 (big ET-3), produced contractile responses in human isolated bronchi, demonstrating the presence of functional endothelin-converting enzyme (ECE) in this tissue. The maximal contractile responses were equal to 108.4+/-8.0% (0.1 microM big ET-1; n=4), 85.2+/-11.8% (0.1 microM big ET-2; n=7) and 43.0+/-7.2% (0.1 microM big ET-3; n=5) of the reference response to acetylcholine (1 mM). The response to big ET-1 (0.1 microM), but not endothelin-1 (ET-1, 0.1 microM), was diminished after overnight storage of the tissue at 4 degrees C, demonstrating instability of the enzyme. The responses to all three big-endothelins were significantly inhibited, by the ECE inhibitors CGS 26393 and CGS 26303, in a concentration-related manner. The responses to the mature peptides ET-1, endothelin-2 (ET-2), and endothelin-3 (ET-3) were unaffected by CGS 26393 and CGS 26303. Phosphoramidon (10 microM) also produced an inhibition of the response to big ET-1 that was equivalent to that produced by CGS 26393 (10 microM). Combination of CGS 26393 (10 microM) and phosphoramidon (10 microM) did not produce an additive inhibition. These results demonstrate the presence of functional ECE for all three big endothelins in human bronchus and inhibition of the enzyme by newly developed orally active ECE inhibitors, as well as phosphoramidon. British Journal of Pharmacology (2000) 129, 170 - 176
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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 | 0.001 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".