Role of the PKC/CPI‐17 pathway in enhanced contractile responses of mesenteric arteries from diabetic rats to <i>α</i>‐adrenoceptor stimulation
Bibliographic record
Abstract
Protein kinase C (PKC) may contribute to enhanced contractile responses of arteries from streptozotocin-diabetic rats to stimulation of G-protein coupled receptors. This was investigated by comparing the effects of PKC inhibitors on contractile responses of mesenteric arteries from diabetic and age-matched control rats to noradrenaline (NA) and endothelin-1 (ET-1). The effects of NA and ET-1 on the distribution of three isoforms of PKC implicated in contraction were also determined. In addition, the effect of NA on phosphorylation of CPI-17, a substrate for PKC, was investigated. Contractile responses of endothelium-denuded arteries from diabetic rats to NA were enhanced, but were normalized by PKC inhibition. In contrast, contractile responses to ET-1 were not significantly different, and were blocked to a similar extent by PKC inhibition, in arteries from control and diabetic rats.NA produced only a small increase in particulate levels of PKCepsilon in control arteries (to 125+/-8% of levels in untreated arteries), but a significant increase in particulate PKCalpha (to 190+/-22%) and a much greater increase in particulate PKCepsilon (to 230+/-19%) in arteries from diabetic rats. ET-1 increased particulate PKCalpha and epsilon to a similar extent in arteries from control and diabetic rats.NA significantly enhanced CPI-17 phosphorylation from a basal level of 22+/-10 to 71+/-7% of total in arteries from diabetic rats, and this was prevented by PKC inhibition. NA had no detectable effect on CPI-17 phosphorylation in arteries from control rats. These data suggest that NA-induced activation of PKC and CPI-17, its downstream target, is selectively enhanced in arteries from diabetic rats, and mediates the enhanced contractile responses to this agonist.
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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) | 0.001 | 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 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".