Enhanced Myosin Phosphatase and Ca2+-Uptake Mediate Adrenergic Relaxation of Airway Smooth Muscle
Bibliographic record
Abstract
We examined the mechanisms underlying relaxations evoked by isoproterenol (Iso) in isolated porcine, bovine, or human tracheal and bronchial tissues (TSM and BSM, respectively). Iso had little effect against contractions evoked by high KCl, indicating that it does not directly suppress voltage-dependent Ca(2+)-influx nor directly inhibit myosin light chain kinase. Furthermore, Iso was equally potent against carbachol (CCh) contractions in the presence versus absence of nifedipine (10(-6) M), establishing that the primary action of Iso is not through membrane hyperpolarization. However, Iso relaxations in porcine/bovine BSM were significantly suppressed by inhibitors of the internal Ca(2+) pump (cyclopiazonic acid; 10(-5) M) or of myosin light chain phosphatase (calyculin; 10(-6) M). Myosin light chain phosphatase activity was assayed directly (using (32)P-labeled myosin) and found to be enhanced in a time- and concentration-dependent fashion by Iso. Iso relaxations in human airway tissues, on the other hand, were not significantly affected by either calyculin or cyclopiazonic acid. Thus, we conclude that Iso acts largely in a voltage-independent fashion: in nonhuman airways, this involves enhanced Ca(2+) pump activity (to decrease [Ca(2+)](i)) and myosin light chain phosphatase activation (to decrease Ca(2+)-sensitivity of the contractile apparatus), whereas in human airways the underlying mechanisms are still unclear.
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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) | 0.000 | 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".