Regulation of nitric oxide synthesis by beta‐adrenergic receptors in the nuclear envelope
Bibliographic record
Abstract
Both β‐adrenergic receptors (β‐ARs) and endothelin receptors (ETRs) have been shown to be present on nuclear membranes in adult cardiac ventricular myocytes. These nuclear‐localized receptors are functional with respect to ligand binding and effector activation. Furthermore, isoproterenol (ISO) increases transcription initiation in isolated nuclei whereas endothelin‐1 (ET‐1) has the opposite effect. Here we investigate whether ISO and ET‐1 regulate nitric oxide (NO) production in nuclear membranes. Isolated nuclei were incubated with a fluorescent NO indicator, 4,5‐diaminofluorescein (DAF‐2), followed by either ET‐1 or ISO treatment. In both cases, an increase in DAF‐2 fluorescence was observed: this increase was inhibited by the NO synthase inhibitor, L‐NAME. Pertussis toxin treatment also increased DAF‐2 fluorescence. The PKB inhibitor triciribine, which converts ISO from an activator of transcription to an inverse agonist, potentiated ISO‐mediated DAF‐2 fluorescence without affecting ET‐1 signalling. These experiments were repeated in intact myocytes using caged analogues of ISO and ET‐1, and in combination with 4,5‐diaminofluorescein diacetate (DAF‐2 DA), a cell‐permeant form of DAF‐2. Our results suggest the nuclear β‐ARs and ETRs regulate NO synthesis.
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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".