Enhanced Neurotrophin Signaling Following Chronic Hypoxia Potentiates Catecholamine Release from Adrenal Chromaffin Cells
Bibliographic record
Abstract
Environmental stressors, including chronic hypoxia, stimulate catecholamine secretion from adrenomedullary chromaffin cells (AMCs); however, the underlying molecular mechanisms remain unclear. Here, we investigated the role of brain‐derived neurotrophic factor (BDNF) signaling in rat AMCs exposed to chronic hypoxia. In rat adrenal glands, BDNF and its tropomyosin‐related kinase B (TrkB) receptor were highly expressed in the cortex and medulla, respectively. Exposure of AMCs to chronic hypoxia (2% O 2 ; 48 hr) in vitro caused a significant increase in TrkB mRNA expression. A similar increase was observed in an immortalized chromaffin cell line (MAH cells); however, it was absent in MAH cells deficient in the transcription factor HIF‐2a. Activation of TrkB with a specific agonist, 7,8 dihydroxyflavone (7,8 DHF), or BDNF on chronically hypoxic (Chox) AMCs increased intracellular Ca 2+ ([Ca 2+ ] i ) and quantal catecholamine release to a greater extent than normoxic (Nox; 21% O 2 ) controls. The TrkB‐induced [Ca 2+ ] i rise was sensitive to the tyrosine kinase inhibitor K252a and nickel, but not the Ca 2+ store‐depleting agent, cyclopiazonic acid. TrkB activation also induced membrane depolarization and action potential firing that occurred with a higher frequency in CHox cells. This was accompanied by a conductance increase, and the spike discharge was inhibited by pyrazole‐3, a selective TRPC3 channel blocker. These data demonstrate that, during chronic hypoxia, enhancement of BDNF‐TrkB signaling increases membrane excitability and extracellular Ca 2+ influx in chromaffin cells, which leads to a marked potentiation in catecholamine secretion. This work was funded by the Natural Sciences and Engineering Research Council. A.S. is a NSERC Post‐doctoral Fellow.
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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) | 0.001 | 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".