Endothelin B Receptor-Mediated Regulation of Endothelin-1 Content and Release in Cultured Porcine Aorta Endothelial Cell
Bibliographic record
Abstract
Several cardiovascular diseases are associated with an increase in circulating levels of endothelin-1 (ET-1). Little is known about the consequences of this increase on endothelial cell responses with respect to ET-1 production and regulation. Confluent, passage 1, cultured porcine aorta endothelial cells were exposed to exogenous ET-1 (0.1 microM) for 24 h. BQ788 (1 microM, ETB receptor antagonist) but not BQ123 (1 microM, ETA receptor antagonist) significantly (p < 0.05) reduced 125I-ET-1 uptake. The effects of BQ788 were mimicked by dansylcadaverine (0.5 mM) but not nystatin (50 microg/ml). Immunoreactive ET-1 endothelial cell content doubled (p < 0.05) after 24 h of exogenous ET-1 treatment. Bosentan (10 microM, dual ETA/B receptor antagonist) reduced (p < 0.05) immunoreactive ET-1 content in control cells. Bosentan prevented exogenous ET-1-induced endothelial cell ET-1 loading, suggesting that exogenous ET-1 is partly recycled. PreproET-1 mRNA levels were reduced (p < 0.05) by exogenous ET-1 after 24 h, an effect blocked by BQ788 and bosentan. When used alone, both receptor antagonists increased mRNA levels. The results of this study suggest that part of ET-1 is recycled through ETB receptors and subsequently released to contribute to constitutive ET-1 overflow. ET-1 exerts a negative feedback on ET-1 gene transcription, which is dependent on ETB receptor activation and internalization of the complex ET-1/ETB receptor. The maintenance of this negative regulatory loop of ET-1 production may be essential for the normal endothelial physiology.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 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 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".