Bile acids stimulate cholangiocyte fluid secretion by activation of transmembrane member 16A Cl− channels
Bibliographic record
Abstract
Bile acids stimulate a bicarbonate‐rich choleresis, in part, through effects on cholangiocytes. Because Cl− channels in the apical membrane of cholangiocytes provide the driving force for secretion and transmembrane member 16A (TMEM16A) has been identified as the Ca2+‐activated Cl− channel in the apical membrane of cholangiocytes, the aim of the present study was to determine whether TMEM16A is the target of bile‐acid–stimulated Cl− secretion and to identify the regulatory pathway involved. In these studies of mouse, rat, and human biliary epithelium exposure to ursodeoxycholic acid (UDCA) or tauroursodeoxycholic acid (TUDCA) rapidly increased the rate of exocytosis, ATP release, [Ca2+]i, membrane Cl− permeability, and transepithelial secretion. Bile‐acid–stimulated Cl− currents demonstrated biophysical properties consistent with TMEM16A and were inhibited by pharmacological or molecular (small‐interfering RNA; siRNA) inhibition of TMEM16A. Bile acid–stimulated Cl− currents were not observed in the presence of apyrase, suramin, or 2‐aminoethoxydiphenyl borate (2‐APB), demonstrating that current activation requires extracellular ATP, P2Y, and inositol 1,4,5‐trisphosphate (IP3) receptors. TUDCA did not activate Cl− currents during pharmacologic inhibition of the apical Na+‐dependent bile acid transporter (ASBT), but direct intracellular delivery of TUDCA rapidly activated Cl− currents. Conclusion: Bile acids stimulate Cl− secretion in mouse and human biliary cells through activation of membrane TMEM16A channels in a process regulated by extracellular ATP and [Ca2+]i. These studies suggest that TMEM16A channels may be targets to increase bile flow during cholestasis. (Hepatology 2018;68:187‐199).
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".