Reduced catecholamine sensitivity is related to a decrease in adenylate cyclase activity mediated by ß1‐adrenergic receptor signaling in aged ventricular myocytes
Bibliographic record
Abstract
The aim of this study was to determine whether reduced sensitivity to catecholamines in aged myocytes results from deficits in ß‐adrenergic receptor (AR) signaling. Contraction amplitudes and intracellular Ca 2+ were measured in field‐stimulated (2 Hz, 37°C, fura‐2) ventricular myocytes isolated from young adult (3 mos) and aged (24 mos) male Fischer 344 rats. The effect of a ß 1 ‐AR agonist (but not a ß 2 ‐AR agonist) on contraction amplitude was greater in young adult compared to aged myocytes; however, Ca 2+ transient amplitudes were similar in both groups. To examine downstream effectors of ß‐AR signaling we assessed the activity of adenylate cyclase and the formation of cAMP. Aged myocytes had smaller increases in contraction and Ca 2+ transient amplitudes in response to forskolin compared to young adult cells. In addition, direct measurement of cAMP showed an age‐related decrease in cAMP formation in response to forskolin. This reduction in adenylate cyclase activity is likely responsible for the age‐related decrease in catecholamine sensitivity as administration of dibutyryl cAMP showed no age bias on contraction or Ca 2+ transient amplitude. Funding: CIHR & HSFNS.
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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".