A robust bioassay of the human bradykinin B<sub>2</sub> receptor that extends molecular/cellular studies: The isolated umbilical vein
Bibliographic record
Abstract
Bradykinin (BK) and kallidin (Lys-BK) are small peptides cleaved from circulating kininogens by proteases called kallikreins. BK-related peptides are vasodilators, increase microvascular permeability and stimulate nociceptors, reproducing the cardinal signs of inflammation. Medicinal chemistry efforts targeted at their widely expressed B2 receptor (B2R), a GPCR, mainly aimed at producing antagonists. The only BK antagonist in clinical use is the peptide icatibant, approved to abort attacks of hereditary angioedema. However, the anti-inflammatory applications of B2R antagonists are potentially wider. While the screening of new compounds relies on in vitro assays, like radioligand binding competition, classical smooth muscle contractility supports pharmacological evaluation in a time scale of several hours and allows determining potency, surmountability, residual agonist activity, specificity and reversibility. Further, the BK B2R antagonists notoriously exhibit species-specific pharmacological profiles. When investigating the first non-peptide B2R antagonist (WIN 64338), I have introduced the contractility assay based on the isolated human umbilical vein to evaluate ligands of the naturally expressed human B2R. Small molecule ligands characterized using the assay include the partial agonist Fujisawa compound 47a or the exquisitely potent competitive antagonist, Pharvaris compound 3. The umbilical vein assay is also useful to verify pharmacologic properties of peptide B2R ligands, such as the carboxypeptidase-activated latent agonist BK-Arg and agonist or antagonist fluorescent probes. Further, the proposed agonist effect of tissue kallikrein on the B2R has been disproved using the vein. This assay has an intermediate level of complexity between cellular and molecular pharmacology on one hand, and in vivo studies on the other.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".