A farnesyltransferase inhibitor attenuated β-adrenergic receptor downregulation in rat skeletal muscle
Bibliographic record
Abstract
Farnesylation represents an essential posttranslational modification of several well-defined proteins implicated in the homologous desensitization of the beta-adrenergic receptor (beta-ADR). The following study examined the effect of a novel farnesyltransferase inhibitor, BMS-191563, on agonist-mediated beta-ADR downregulation in skeletal muscle. Female Sprague-Dawley rats were treated for 12 days with the beta2-adrenergic agonist clenbuterol (4 mg/kg) with or without the concurrent administration of BMS-191563 (2 mg x kg(-1) x day(-1)). Clenbuterol promoted gastrocnemius muscle hypertrophy, whereas the soleus muscle was unaffected. Total beta-ADR density was decreased by 45 and 40% in the soleus and medial gastrocnemius (MG), respectively, after clenbuterol treatment. BMS-191563 treatment did not prevent clenbuterol-stimulated MG hypertrophy, but markedly attenuated beta-ADR downregulation in both muscle types. This latter effect in the soleus muscle was not associated with the inhibition of Ras farnesylation. Likewise, in rat cardiac fibroblasts, isoproterenol-mediated decrease of total beta-ADR density was abrogated by the prior treatment with BMS-191563. Collectively, these data demonstrate that the mechanism(s) implicated in agonist-mediated beta-ADR downregulation was sensitive to BMS-191563, thereby suggesting the involvement of farnesylated proteins.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".