MRP4 and MRP5 in the ciliary epithelium of the eye and their potential role in regulating extracellular cAMP levels
Bibliographic record
Abstract
The purpose was to determine if the ciliary epithelium expresses multidrug resistance‐associated proteins (MRPs) that transport cyclic nucleotides, and if their activity can influence extracellular cAMP levels. MRP4 and MRP5 were detected in human ciliary body by microarray. mRNAs (RT‐PCR) for both transporters were also detected in a human ciliary epithelial (CE) cell line. Activity for MRP4/5 in CE cells was assessed using monochlorobimaneglutathione. The intracellular accumulation of monochlorobimaneglutathione increased dose‐dependently in the presence of the MRP inhibitors: indomethacin, probenecid, ibuprofen and furosemide. Treatment of CE cells with isoproterenol (100 μM) and IBMX (500 μM) increased intracellular cAMP levels 4.8‐fold (4.1 to 19.7 pmoles/10 6 cells) and extracellular cAMP 5.8‐fold (2.7 to 15.6 nM). The β‐adrenergic stimulation of extracellular cAMP levels was reduced 27–46% by ibuprofen, furosemide and probenecid (500 μM each), whereas indomethacin (500 μM) nearly prevented it completely (94%). MRP4/MRP5 activity may play an important role in aqueous humor dynamics through modulation of the extracellular cAMP‐adenosine signaling pathway. Funding: CIHR, NSERC and NIH.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| 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 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".