Purinergic stimulation of carotid body efferent glossopharyngeal neurones increases intracellular Ca<sup>2+</sup> and nitric oxide production
Bibliographic record
Abstract
New Findings What is the central question of this study? Nitric oxide is a strong modulator of carotid body (CB) chemoreceptor activity; however, the mechanisms leading to the production/release of NO during CB chemoexcitation remained largely unknown. What is the main finding and what is its importance? In the present study, we identified an important contribution of ATP and purinergic P2X receptor signalling in initiating the events leading to NO synthesis and release in efferent neurons to the CB. Acting via P2X receptors, ATP causes an increase in intracellular Ca 2+ that triggers NO production in efferent neurones to the rat carotid body. In addition, ATP‐induced depolarization of these neurones activates voltage‐gated Ca 2+ channels that further amplify the NO inhibitory signal. The mammalian carotid body (CB) is a peripheral chemosensory organ that controls ventilation and is innervated by both afferent and efferent nerve fibres. The afferent pathway is stimulated by chemoexcitants, such as hypoxia, hypercapnia and acidosis. The efferent pathway causes inhibition of the sensory discharge via release of NO that originates mainly from neuronal nitric oxide synthase (nNOS)‐positive autonomic neurones within the glossopharyngeal nerve (GPN). Recent studies in the rat indicate that these inhibitory GPN neurones and their processes express purinergic P2X receptors and can be activated by ATP, a key excitatory CB neurotransmitter. Here we tested the hypothesis that purinergic agonists stimulate a rise in [Ca 2+ ] i , leading to nNOS activation and NO production in isolated GPN neurones, using the fluorescent probes fura‐2 and 4‐amino‐5‐methylamino‐2′,7′‐difluorofluorescein diacetate (DAF‐FM DA), respectively. ATP caused a dose‐dependent increase in [Ca 2+ ] i in GPN neurones (EC 50 ≈ 1.92 μ m ) that was markedly inhibited by a combination of 100 μ m suramin (a non‐specific P2X blocker) and 100 n m Brilliant Blue G (a selective P2X7 blocker). ATP also stimulated NO production in GPN neurones, as revealed by an increase in DAF fluorescence; this NO signal was inhibited by purinergic blockers, chelators of extracellular Ca 2+ , the nNOS inhibitor l ‐NAME and the NO scavenger carboxy‐PTIO. The P2X2/3 and P2X7 agonists α,β,‐methylene ATP and benzoyl ATP mimicked the effects of ATP. Taken together, these data indicate that ATP may contribute to negative feedback inhibition of CB sensory discharge via purinergic stimulation of NO production in efferent fibres.
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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) | 0.000 | 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 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".