5‐Hydroxytryptamine contributes significantly to a reflex pathway by which the duodenal mucosa protects itself from gastric acid injury
Bibliographic record
Abstract
Although duodenal mucosal bicarbonate secretion (DMBS) is currently accepted as an important defense mechanism against acid‐induced duodenal injury, the mechanism and the regulation of DMBS are largely unknown. 5‐HT may regulate DMBS, but little is known about its physiological relevance in DMBS and the underlying mechanism(s). Thus, the aims of the present study were to demonstrate the role of 5‐HT in acid‐stimulated DMBS and to further elucidate the precise mechanisms involved in this process. Luminal acid stimulation significantly increased 5‐HT release from the duodenal mucosa ( P <0.01). SB204070, a selective 5‐HT4 receptor antagonist, dose‐dependently reduced luminal acid‐stimulated HCO 3 ‐ secretion of onstrated to be involved in regulating this physiological mice in vivo. In Ussing chamber studies, 5‐HT‐induced Isc and DMBS were abolished by removal of extracel‐ lular Ca 2+ , and significantly attenuated by pharmaco‐ logical blockade of the Na + /Ca 2+ exchanger (NCX), intermediate Ca 2+ ‐activated K+ channels (IKCa), or cystic fibrosis transmembrane conductance regulator (CFTR). 5‐HT increased cytoplasmic free calcium ([Ca 2+ ]cyt) in SCBN cells, a duodenal epithelial cell line, and knockdown of NCX1 proteins with a specific siRNA greatly decreased this 5‐HT‐mediated Ca 2+ sig‐ via both cytoplasmic free Ca 2+ ([Ca 2+ ]) ‐ and cAMP‐ naling. Taken together, our data suggest that 5‐HT plays a physiological role in acid‐stimulated DMBS via a Ca 2+ signaling pathway, in which the plasma membrane NCX transporter as well as IKCa and CFTR channels may be involved.—Smith, A. J., Chappell, A. E., Buret, A. G., Barrett, K. E., Dong, H. 5‐Hydroxytryptamine (5‐HT) contributes significantly to a reflex pathway by which the duodenal mucosa protects itself from gastric acid injury. FASEB J. 20, 2486–2495 (2006)
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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 | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".