The in vitro transport kinetics of organic anion transporter 1 (OAT1) are influenced by Na‐dependent dicarboxylate cotransporter 3 (NaDC3)
Bibliographic record
Abstract
In vitro studies that assess OAT1 activity study the protein in isolation, despite its reliance on NaDC3. The purpose was to determine if NaDC3 can influence OAT1 activity in typical in vitro assays used during the course of drug development. The uptake of [ 3 H]para‐aminohippurate was determined in Chinese hamster ovary (CHO) cells stably expressing OAT1 (CHO‐OAT1) and CHO‐OAT1 cells transiently transfected with NaDC3. The uptake of PAH was stimulated 2‐fold in the presence versus absence of NaDC3. The NaDC3 inhibitor lithium (2 mM) had little to no effect on OAT1‐mediated PAH transport. The maximal rate of OAT1‐mediated PAH transport increased 3.6‐fold in the presence of NaDC3 (16 vs. 57 pmol/mg protein/min). There was a modest increase in the Michaelis constant associated with PAH transport (0.72 vs. 1.5 μM). The inhibitory potential of probenecid was not affected by co‐expression of NaDC3 (IC50: 4.5 vs. 4.6 μM). In vitro studies with OAT1 should consider examining its activity in the presence of NaDC3. This may be particularly important when using OAT1 kinetic data for in vitro in vivo extrapolation (IVIVE). Funding: NSERC
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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 | 0.001 | 0.001 |
| 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) | 0.002 | 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".