Does chronic stimulation of both nicotinic and opioid receptors contribute to the loss of O2 and CO2 sensitivity in perinatal adrenomedullary chromaffin cells?
Bibliographic record
Abstract
Adaptation of the neonate to extrauterine life depends critically on catecholamine secretion (CAT) from adrenomedullary chromaffin cells (AMC). This CAT secretion is triggered by asphyxial stressors (e.g. hypoxia and hypercapnia) associated with the birthing process and these act directly on AMC, prior to functional splanchnic innervation. These sensing mechanisms are lost postnatally along a time course correlating roughly with innervation of AMC. Thus, the majority of juvenile AMC (>14 days) are unable to sense directly hypoxia and hypercapnia, although there is evidence that these properties may return following denervation. The splanchnic nerve releases various neurotransmitters including acetylcholine (ACh) which activate nicotinic ACh receptors (nAChR) and enkephalins which activate opioid receptors on AMC. Here, we test the hypothesis that activation of these receptors may initiate a signaling cascade leading to the loss of O 2 and/or CO 2 sensitivity. Recently, we showed that chronic stimulation of nAChR on AMC with nicotine, results in the loss of hypoxic, but not hypercapnic, sensitivity ( Buttigieg et al. FASEB J 2007, in press ). This loss of hypoxic sensitivity appears to be mediated by up‐regulation of K ATP channels, which are activated by low PO 2 . Preliminary studies based on exposure of AMC to chronic opioid receptor stimulation suggest that this treatment leads to loss of both hypercapnic and hypoxic sensitivity. Thus, synaptic stimulation of opioid and nACh receptors on AMC may contribute to the normal developmental loss of O 2 and CO 2 sensitivity. Funded by: The Heart and Stroke Foundation (HSF) of Ontario. JB and SB were funded by a Focus on Stroke award from HSF of Canada.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".