Effects of Staurosporine on the Pressor Responses to Alpha-Adrenoceptor Agonists in Pithed Rats: A Comparison with Nifedipine
Bibliographic record
Abstract
The effects of the calcium channel antagonist nifedipine and the protein kinase C (PKC) inhibitor, staurosporine were examined on the pressor actions of a full, cirazoline, and a partial, St587, alpha 1-adrenoceptor agonist as well as the alpha 2-adrenoceptor agonist B-HT 920 in the pithed rat preparation. Administration of nifedipine or staurosporine significantly reduced the diastolic blood pressure of pithed rats. Staurosporine displaced the dose-diastolic pressure response curves for B-HT 920 and St587 to the right in a dose-dependent manner. The ED50 value for the dose-response curves to B-HT 920 and St587 were found to be significantly increased after the administration of staurosporine. Staurosporine also caused a depression of the maximum response to B-HT 920 and St587. The presence of nifedipine resulted in an increase in the ED50 value of the dose-response curve to B-HT 920 and St587, and this was accompanied by significant reductions of the maximum response, whereas the administration of either staurosporine or nifedipine did not significantly affect the calculated ED50 value of the dose-response curve to cirazoline. In the presence of the calcium channel antagonist but not the PKC inhibitor the maximum response to cirazoline was significantly depressed. As judged from the slope function of the dose-response curves the nature of the inhibition produced by nifedipine compared to staurosporine also appeared to differ. Thus, with nifedipine as the antagonist, the slope function of the dose-response curve for alpha-agonists was significantly reduced. Moreover, in contrast to the actions of staurosporine, nifedipine reduced the maximum response to cirazoline in a dose-independent manner. This study supports the hypothesis that activation of alpha-adrenoceptors that have a substantial dependence on extracellular calcium for vasoconstriction are susceptible not only to the action of calcium channel antagonists but also to the actions of the PKC inhibitor staurosporine, thus suggesting that PKC may modulate directly/indirectly calcium channel activity in vascular smooth muscle.
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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) | 0.001 | 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) | 0.000 | 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".