Influences of Indomethacin on Contractions Induced by Endothelins in Guinea Pig Isolated Gallbladder
Bibliographic record
Abstract
Endothelins (ETs) potently contract guinea pig gallbladder (GPGB) via endothelin-A and -B (ETA and ETB) receptors. This study assesses the possible participation of eicosanoids in the mediation of responses of the GPGB (Krebs' solution, 37 degrees C, 0.5 g load) triggered through each receptor type. Indomethacin (INDO; 5.6 microM) shifted the curve to endothelin-1 (ET-1) (0.1-100 nM) to the right, enhancing the CK50 (concentration causing 50% of response to KCl 80 mM) from 0.9 to 6.8 nM and reducing its EH (response to 100 nM) from 170 +/- 13 to 123 +/- 9 (% of response to 80mM KCl). INDO strongly depressed responses to sarafotoxin S6c (S6c; control CK50 0.9 nM), reducing its EH from 108 +/- 5 to 21 +/- 4. Neither BQ-123 nor BQ-788 (1 microM) changed responses to ET-1, but each markedly reduced responsiveness to ET-3 (control: CK50 of 9.7 nM and EH of 153 +/- 14; BQ-123: approximately = 100 nM and 44 +/- 12; BQ-788 approximately = 100 nM and 65 +/- 18). In the presence of BQ-123, INDO further depressed responses to ET-3 (EH 26 +/- 6), whereas in the presence of BQ-788, such responses were strongly enhanced (EH 126 +/- 9). These findings strongly suggest that contractions of GPGB caused via ETB receptors are mediated to a large extent by contractile eicosanoids, whereas those caused (at least by ET-3) via ETA receptors are limited by relaxant eicosanoids. The cellular sources and nature of the eicosanoids released by ETs remain to be established.
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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".