Propofol-induced Inhibition of Catecholamine Release Is Reversed by Maintaining Calcium Influx
Bibliographic record
Abstract
AbstractAbstract Clinically relevant concentrations of propofol (10 to 30 μM) indeed inhibited the depolarization (by K + )-dependent norepinephrine release in cultured PC12 cells (which are derived from rat adrenal chromaffin cells) and synaptosomes. Unexpectedly, the same propofol concentrations that inhibited depolarization-dependent norepinephrine release increased ionomycin (a Ca 2+ ionophore)-triggered catecholamine release in a Ca 2+ -dependent manner. The Ca 2+ -dependent propofol-induced increase in ionomycin-triggered catecholamine release was abolished in the presence of the Ca 2+ chelator, EGTA. Background Propofol (2,6-diisopropylphenol) is one of the most frequently used anesthetic agents. One of the main side effects of propofol is to reduce blood pressure, which is thought to occur by inhibiting the release of catecholamines from sympathetic neurons. Here, the authors hypothesized that propofol-induced hypotension is not simply the result of suppression of the release mechanisms for catecholamines. Methods The authors simultaneously compared the effects of propofol on the release of norepinephrine triggered by high K + -induced depolarization, as well as ionomycin, by using neuroendocrine PC12 cells and synaptosomes. Ionomycin, a Ca 2+ ionophore, directly induces Ca 2+ influx, thus bypassing the effect of ion channel modulation by propofol. Results Propofol decreased depolarization (high K + )-triggered norepinephrine release, whereas it increased ionomycin-triggered release from both PC12 cells and synaptosomes. The propofol (30 μM)-induced increase in norepinephrine release triggered by ionomycin was dependent on both the presence and the concentration of extracellular Ca 2+ (0.3 to 10 mM; n = 6). The enhancement of norepinephrine release by propofol was observed in all tested concentrations of ionomycin (0.1 to 5 μM; n = 6). Conclusions Propofol at clinically relevant concentrations promotes the catecholamine release as long as Ca 2+ influx is supported. This unexpected finding will allow for a better understanding in preventing propofol-induced hypotension.
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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 | 0.001 |
| 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 | 0.001 |
| 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".