Compensatory upregulation of the adenosine system following phenylephrine-induced hypertrophy in cultured rat ventricular myocytes
Bibliographic record
Abstract
Adenosine has been shown to exert direct antihypertrophic effects on the heart, and plasma adenosine levels have been shown to be elevated in patients with heart failure. It has therefore been proposed that endogenously synthesized adenosine may function as a cardiac antihypertrophic factor. The present study was aimed to determine whether the adenosine system is altered in a potential adaptive manner following phenylephrine-induced hypertrophy in cultured neonatal rat ventricular myocytes. Phenylephrine produced significant hypertrophy as determined by cell size and atrial natriuretic peptide gene expression, which was accompanied by significantly increased gene and protein expression of adenosine A(1), A(2a), and A(3) receptors. These effects and the hypertrophic response were prevented by the alpha(1)-adrenoceptor antagonist prazosin as well as pharmacological agonists for all adenosine receptor subtypes. The upregulation of adenosine receptors by phenylephrine was also abrogated by adenosine 5'-(alpha,beta-methylene)diphosphate, an inhibitor of ectosolic 5'-nucleotidase. Moreover, phenylephrine significantly increased production of adenosine from myocytes in the presence of a nucleoside transport and adenosine deaminase inhibitor, the combination of which abrogated the hypertrophic effect of phenylephrine. The latter effect was reversed by adenosine receptor antagonists. Phenylephrine also produced a significant upregulation in expression levels of equilibrative nucleoside transporter 1 although expression levels of equilibrative nucleoside transporter 2 were unaffected. Taken together, our results suggest an adaptive upregulation of the adenosine system to phenylephrine-induced cardiomyocyte hypertrophy that serves to limit the hypertrophic effect of alpha(1-)adrenoceptor activation.
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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 | 0.001 |
| 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".