An estimation of β<sub>2</sub>‐adrenoceptor reserve on human bronchial smooth muscle for some sympathomimetic bronchodilators
Bibliographic record
Abstract
BACKGROUND AND PURPOSE: The beta(2)-adrenoceptor on human pro-inflammatory cells is exquisitely sensitive to desensitization, whereas beta(2)-adrenoceptor-mediated relaxation of human airways smooth muscle (HASM) is relatively resistant to this phenomenon. An explanation for this discrepancy is that a large beta(2)-adrenoceptor 'reserve' exists on HASM cells for sympathomimetic bronchodilators, which protects against desensitization. EXPERIMENTAL APPROACH: The operational model of agonism was used to estimate the affinity of salbutamol, terbutaline, formoterol and procaterol for the beta(2)-adrenoceptors in methacholine (MCh)-contracted HASM from which the relationship between fractional receptor occupancy and relaxation was determined. This analysis was performed under conditions of fractional, irreversible, beta(2)-adrenoceptor inactivation and, for salbutamol and terbutaline only, by the comparative method of Barlow et al. The affinity of salbutamol for the beta(2)-adrenoceptor guinea-pig eosinophils and the receptor/occupancy-response relationship for the suppression of the respiratory burst (an index of pro-inflammatory cell function) was also determined. KEY RESULTS: For salbutamol and terbutaline, both pharmacological approaches yielded in HASM discrepant affinity estimates (values differed, maximally, by 0.67 log(10) unit). However, affinity values more closely agreed (difference <0.47 log(10) unit), when operational analysis was performed on data corrected for 'fade' of the MCh-induced contraction. Plots of fractional beta(2)-adrenoceptor occupancy versus relaxation indicated a receptor 'reserve' for all agonists tested at all levels of response. In contrast, minimal receptor reserve was detected for the ability of salbutamol to suppress respiratory burst activity in eosinophils. CONCLUSIONS AND IMPLICATIONS: These data may help explain the relative inability of sympathomimetic bronchodilators to render HASM tolerant to beta(2)-adrenoceptor-mediated relaxation.
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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 | 0.001 | 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 | 0.000 |
| 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 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".