Internalization and trafficking of opioid receptor ligands in rat cortical neurons
Why this work is in the frame
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Bibliographic record
Abstract
The binding, internalization, and trafficking of the fluorescently labeled opioid peptides Fluo-dermorphin and Fluo-deltorphin were quantitatively studied by confocal microscopy in primary cortical neurons in culture. Specific binding of these selective ligands to neurons naturally expressing mu (mu) and delta (delta) opioid receptors (OR), respectively, resulted in their internalization into neuronal somas and processes, as indicated by the persistence of fluorescent labeling following removal of cell surface binding by hypertonic acid wash. This internalization was receptor-specific, as the fluorescent signal was completely abolished when the cells were concomitantly incubated with the opioid receptor antagonist naloxone. It also was clathrin-dependent, as it was totally prevented by the endocytosis inhibitor phenylarsine oxide. Accordingly, internalized ligands were detected inside small, endosome-like vesicles. These labeled vesicles accumulated within nerve cell bodies between 5-30 min of incubation with the fluorescent ligands. This accumulation was abolished after treatment with the antitubular agent nocodazole, suggesting that it was due to a microtubule-dependent, retrograde transport of the internalized ligands from processes to the soma. By contrast, there was no change in the compartmentalization of internalized (mu)OR or deltaOR, as assessed by immunocytochemistry, suggesting that the latter were recycled locally. The present results provide the first demonstration of receptor-mediated internalization of opioid peptides in cultured neurons. It is proposed that their retrograde transport into target cells might be involved in mediating some of the long-term, transcriptional effects of opioids.
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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) | 0.000 | 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 it