Characterization of Ectonucleotidase Expression in the Rat Carotid Body: Potential Regulation by Hypoxia?
Bibliographic record
Abstract
The carotid body (CB) maintains homeostasis in the respiratory and cardiovascular systems of mammals by initiating reflex responses during exposures to blood‐borne stimuli such as low O 2 (hypoxia). Thus, stimulation of CB chemoreceptors during hypoxia results in compensatory hyperventilation and activation of the sympathoadrenal system. CB hyperactivity has been linked to several clinical morbidities including sleep apnea, chronic obstructive pulmonary disease, hypertension, obesity, and heart failure. The purine ATP and its derivative, adenosine, contribute significantly to the excitatory CB afferent discharge during hypoxia ( Conde et al., 2012, J Appl Physiol 112: 2002–10; Nurse and Piskuric, 2013, Semin Cell Dev Biol 24: 22–30 ). Given that extracellular nucleotides and products of their hydrolysis by ectonucleotidases are known to play a key role in purinergic signaling in the brain and tissues innervated by the autonomic nervous system, we investigated ectonucleotidase expression in the rat CB. Ectonucleoside triphosphate diphosphohydrolase (E‐NTPDase) is the dominant family of ectonucleotidases and subtypes of this enzyme family catalyze the hydrolysis of purines and regulate their levels in the synaptic cleft. In extracts of whole rat CBs, RT‐PCR and sequence analyses revealed the presence of E‐NTPDase‐1 and ‐2, as well as ecto‐5′‐ectonucleotidase (Nt5e) mRNA. Interestingly, expression of ectonucleotidases, E‐NTPDase‐1 (CD39) and Nt5e (CD73), has been proposed to have a protective role in mouse intestinal epithelia during hypoxia ( Synnestvedt et al., 2002, J Clin Invest 110: 993–02 ). This raised the possibility that ectonucleotidases might be regulated by hypoxia in O 2 ‐sensitive organs such as the CB and its neural crest‐derived counterpart, the adrenal medulla. Indeed, microarray analysis of a rat O 2 ‐sensitive immortalized adrenomedullary chromaffin cell line (MAH cells) suggests that chronic hypoxia exerts a selective hypoxia inducible factor‐2 alpha (HIF2a)‐dependent upregulation of E‐NTPDase‐2 transcript. Future studies will determine the cellular localization of ectonucleotidases in the rat CB and the potential role of HIF2a in the regulation of E‐NTPDase‐2 expression during chronic hypoxia. Support or Funding Information Supported by grants from Canadian Institutes of Health Research and Natural Sciences and Engineering Research Council 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) | 0.000 | 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".