Characterization of bidirectional adenosine transporters in rat brain synaptosomes and clonal DDT|1 MF-2 smooth muscle cells using [3H]L-adenosine
Bibliographic record
Abstract
Membrane-bound nucleoside transport processes and their inhibitors regulate intra- and extra-cellular levels of endogenous D-adenosine and the actions of adenosine are mediated through adenosine receptors. Our research involved (1) developing a method to measure adenosine transport and release in animal cells and CNS tissue, (2) characterizing the transport processes involved, and (3) determining the effects of transport inhibitors on these processes. Using rat brain synaptosomal preparations we showed that ($\\sp3$H) L-adenosine, the metabolically stable enantiomer of ($\\sp3$H) D-adenosine, was released in a concentration- and time-dependent, and temperature-sensitive manner that was linear with synaptosomal protein content. Release of ($\\sp3$H) L-adenosine was inhibited by the nucleoside transport inhibitors dipyridamole, nitrobenzylthioinosine (NBI) and dilazep, as well as unlabelled L-adenosine, D-adenosine and uridine, suggesting that release occurred at least in part by NBI-sensitive equilibrative nucleoside transporters. To determine further which subtype of equilibrative nucleoside transporter was involved, we conducted similar studies using cells, DDT$\\sb1$ MF-2 cells, that contain only NBI-sensitive (es) nucleoside transporters. In DDT$\\sb1$ MF-2 cells, accumulation of ($\\sp3$H) D-adenosine was more rapid than that of ($\\sp3$H) L-adenosine. ($\\sp3$H) D-Adenosine uptake was inhibited by unlabelled L-adenosine to a greater degree than ($\\sp3$H) L-adenosine uptake was inhibited by unlabelled D-adenosine. Nitrobenzylthioinosine inhibited uptake of ($\\sp3$H) D- and ($\\sp3$H) L-adenosine. ($\\sp3$H) L-Adenosine release was temperature- and time-dependent, and was inhibited by NBI. Our studies support the use of ($\\sp3$H) L-adenosine as a useful probe for the characterization adenosine transport and release, and show that release occurs in part by nucleoside transporters that are sensitive to inhibition by nanomolar concentrations of NBI. Such studies may help identify therapeutically useful adenosine transport inhibitors.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".