Pyridoxal-5′-phosphate (MC-1), a vitamin B6 derivative, inhibits expressed P2X receptors
Bibliographic record
Abstract
P2X receptors are cation-permeable ligand-gated ion channels that open in response to the binding of ATP. These receptors are present in many excitable cells, including neurons, striated muscle cells, epithelial cells, and leukocytes. They mediate fast excitatory neurotransmission in the central and peripheral nervous systems and are thought to be involved in neuropathic pain, inflammation, and cell damage following ischemia-reperfusion injuries. P2X receptors are thus a target for the development of new therapeutics to treat chronic pain and inflammation. In this study, we characterized the inhibition caused by pyridoxal-5'-phosphate, a natural metabolite of vitamin B6 (MC-1), of P2X₂, P2X₄, P2X₇, and P2X₂/₃ receptors stably expressed in HEK293 cells using the patch-clamp technique in the whole-cell configuration. We also tested a new approach using VC6.1, a modified cameleon calcium-sensitive fluorescent protein, to characterize the inhibition of P2X₂ and P2X₂/₃. MC-1 blocked these two P2X receptors, with an IC₅₀ of 7 and 13 μmol/L, respectively. P2X₂ exhibited the highest affinity for VC6.1, and the chimeric receptor P2X₂/₃, the lowest. The patch-clamp and imaging approaches gave similar results and indicated that VC6.1 may be useful for high throughput drug screening. Pyridoxal-5'-phosphate is an efficient P2X blocker and can be classified as a P2X antagonist.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.003 | 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 teacher head, 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".