Receptors Mediating Endothelin-1-Induced Contractions of Rabbit Gallbladder
Bibliographic record
Abstract
We have examined the responsiveness of strips of rabbit gallbladder (RGB) to endothelin (ET) receptor agonists, and its susceptibility to blockade by selective antagonists. Endothelin-1 (ET-1; 0.1-100.0 nM) caused graded tonic contractions with a CK50 (concentration causing response equivalent to 50% of KCl 80 mM) of 3.4 nM and EH (response to highest concentration) of 186 +/- 22, being 40-fold less potent than cholecystokinin-8 (CCK-8), 103-fold more potent than carbachol, but equipotent to ET-3, sarafotoxin S6c (S6c) and IRL 1620. The selective ETA receptor antagonists BQ-123 (3 microM) and A-127722-5 (0.3 microM) did not block responses to ET-1, but BQ-123 depressed responses to 30-100 nM ET-3 by about 35%. The ETB receptor antagonist BQ-788 (1 microM) shifted the curve to S6c by only fivefold. In rabbit aorta and at these same concentrations, BQ-123 and A-127722-5 markedly shifted (> or = 100-fold) the curve for ET-1-induced contraction, whereas BQ-788 shifted that for S6c 40-fold. Higher concentrations of all three antagonists contracted the RGB. Thus, although RGB responses to ETs and selective ETB receptor agonists seem to be largely mediated via ET, receptors, they are remarkably insensitive to blockade by both selective ETA and ETB receptor antagonists, as previously reported in the guinea pig gallbladder. Finally, through yet unknown mechanisms, high concentrations of ET receptor antagonists induce marked RGB contractions. It remains to be seen whether this finding is predictive of adverse biliary tract side-effects of such drugs in the clinic.
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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 | 0.000 | 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) | 0.002 | 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 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".