Characterization of B‐9972, a peptidase‐resistant agonist of the bradykinin B2 receptors: effects on the endocytosis and recycling of the receptors
Bibliographic record
Abstract
The bradykinin (BK) B 2 receptor (B 2 R) is a good model of a G protein coupled receptor regulated by a cycle of phosphorylation, endocytosis and extensive recycling at the cell surface following agonist stimulation. B‐9430 (D‐Arg‐[Hyp 3 , Igl 5 , D‐Igl 7 , Oic 8 ]‐BK) is a second generation peptide antagonist found to be competitive at the human B 2 R and insurmountable at the rabbit B 2 R (contractility assays, isolated human umbilical and rabbit jugular veins). Two isomers of this peptide were prepared: B‐10344 (inverted sequence Oic 7 , D‐Igl 8 ) and B‐9972 (Oic 7 ‐Igl 8 ); respectively low and high affinity agonists of the B 2 R. Two functional chimerical constructions based on the rabbit B 2 R were exploited to compare the effects of different agonists on receptor cycling: a green fluorescent protein conjugate (B 2 R‐GFP) and the novel N‐terminal tagged myc‐B 2 R. Imaging and immunoblotting showed that B‐9972 induced a persistent endocytosis of cell surface B 2 Rs in HEK 293 cells with a slow receptor degradation (weak after 3 hours of treatment, important at 12 hours). BK combined with captopril reproduced a part of the effects of B‐9972 on B 2 R downregulation. B‐9430 reduces the morphological effects and downregulation of B 2 Rs by the agonists, although B‐9430 exerted some partial agonist effects on recombinant receptors expressed at high densities (calcium transients, etc.). The results illustrate the agonist‐antagonist transition in B 2 R peptide ligands with constrained C‐terminal structures, the importance of species of origin for their pharmacological profile and the possibility of downregulating receptors selectively using a peptidase‐resistant agonist.
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 | 0.000 | 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) | 0.001 | 0.001 |
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".