Adenosine A <sub>3</sub> Receptor Expression and Function in Mitochondria
Bibliographic record
Abstract
Mitochondrial dysfunction is emerging as a common mechanism of a variety of neurodegenerative diseases, including chemotherapy‐induced neuropathic pain. We have recently found that administration of selective agonists to the G protein‐coupled, adenosine A 3 receptor (A 3 AR) prevents the development of chemotherapy‐induced mitochondrial dysfunction in peripheral sensory neurons that result peripheral neuropathy and chronic pain. Recent evidence also indicates the presence of G proteins and G‐coupled protein receptors within mitochondria, including the adenosine A 1 and A 2A receptors. Bioinformatic analysis revealed potential mitochondrial‐associated sequences in published A 3 AR protein sequences, thus prompting us to hypothesize that A 3 AR is associated with mitochondria and its signaling could regulate mitochondrial function. Using Western blot analysis and transmission immune‐electron microscopy, we report for the first time that A 3 AR is present in normal rat mitochondria purified from liver, spinal cord and peripheral blood lymphocytes. Moreover, we also report that when normal rodent mitochondria are pretreated with the selective A 3 AR agonist, MRS5890, they produced more ATP following ADP‐stimulation than mitochondria treated with its vehicle (0.002% DMSO). We also find that MRS5980 counteracts normal mitochondrial membrane depolarization during calcium mobilization. Collectively, our data provide the first evidence for the presence A 3 AR in mitochondria and initial mechanistic insight to its functional role in mitochondria that potentially could serve as a target for the treatment of neurodegenerative disease. Support or Funding Information NIH‐NCI CA169519
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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 | 0.000 | 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".