Activation of cAMP-Dependent Protein Kinase in Rat Aorta by cAMP Analogs Is Not Correlated with Relaxation
Bibliographic record
Abstract
The role of cAMP-dependent protein kinase (PKA) in the relaxation of vascular smooth muscle by cAMP analogs was studied. The analog N6,2'-O-dibutyryl-cAMP (dbu-cAMP) reduced KCl- and phenylephrine (PE)-induced tension in rat aortic rings in a dose-dependent fashion (10-100 microM). Conversely, incubation with 8-bromo-cAMP (8Br-cAMP; 10-100 microM) had very little effect on tension. The soluble and particulate PKA activity was determined in the analog-treated, PE-contracted tissue. Interference from extracellular analogs was eliminated by washout of analog prior to homogenization of the tissue for the PKA assay and by the addition of charcoal (10 mg/ml) to the homogenization buffer. The nonrelaxant analog 8Br-cAMP significantly increased the activity ratio of soluble PKA at a concentration of 30 microM and, in the particulate fraction, increased the activity ratio at 30- and 100 microM. Total PKA activity in the soluble fraction was significantly decreased by all concentrations of 8Br-cAMP used (10, 30, 100 microM). The relaxant analog dbu-cAMP had no significant effect at any concentration on catalytically active or total PKA activity levels. The only effect seen, at 30 microM, was an increase in the particulate activity ratio, and this was smaller than that seen with 8Br-cAMP. The basis for the alteration in PKA activity by 8Br-cAMP was a decrease in total soluble PKA activity as opposed to an increase in free catalytic PKA subunit. The fall in total activity was most likely due to adsorption by charcoal of catalytic subunit released from the 8Br-cAMP-activated holoenzyme. Thus, under the conditions used to assay PKA activity in cAMP-analog-treated vascular tissue, a decrease in total PKA activity represents an activation of the enzyme and, in fact, appears to be a better indicator of activation than changes in activity ratios. In either case, activation of soluble and particulate PKA by cAMP analogs did not correlate with relaxation of rat aortic rings.
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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) | 0.002 | 0.001 |
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".