Salicylic acid alters endothelin-1 binding in intact adult rat ventricular myocytes
Bibliographic record
Abstract
Endothelin receptors ET(A)R and ET(B)R form tight receptor-ligand complexes that complicate our understanding of the physiological, pharmacological, and biochemical properties of these receptors. Although radioligand-binding studies have demonstrated the binding of endothelin-1 (ET-1) to ET(A)R to be essentially irreversible, ET(A)R internalize in a ligand-dependent manner, release ET-1, and then recycle to the cell surface. Salicylic acid (SA) reduces ET-1 binding (IC(50) = 10 mmol/L) to recombinant ET(A)R in isolated membranes by promoting dissociation of [(125)I]ET-1. In the present study, SA (5 mmol SA/L) did not alter [(125I)]ET-1 binding to intact adult rat ventricular myocytes. The lack of effect was not due to internalization of receptor-ligand complexes. However, 100 mmol SA/L significantly reduced [(125)I]ET-1 binding to both intact myocytes and isolated membranes. SA induced the phosphorylation p42/44 extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase and an unidentified 40-kDa protein on the activating threonine-glutamic acid-tyrosine (T-E-Y) motif. ERK phosphorylation was reduced by a MAP kinase kinase (MEK) inhibitor, PD98059. Phosphorylation of p40 was reduced by the p38 MAP kinase inhibitor SB203580, but not PD98059. However, inhibition of ERK or p38 MAP kinases did not alter the ability of 100 mmol SA/L to induce dissociation of [125I]ET-1. These results suggest that, in the ventricular myocyte, salicylic acid alters the kinetics of ET-1 binding. The results also suggest an allosteric binding site may be present that modulates the dissociation of ET-1 receptor-ligand complexes in response to an as-of-yet unidentified mediator.
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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 | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".