Desensitization of vascular endothelin receptors by G protein-coupled receptor kinase 2
Bibliographic record
Abstract
At the heart of receptor-mediated signal transduction are two intertwined processes: translation of signals carried by stimulating agents to cells through intracellular messenger molecules and termination/restriction of signalling by cells. The latter is a critical mechanism that protects cells from overreacting to an extended or appropriate stimulus and makes cells ready to react to forthcoming stimulation. G protein-coupled receptors (GPCRs) are a family of receptors composed of seven transmembrane domains that respond to various stimuli. GPCRs usually undergo rapid desensitization after activation, in which GPCR kinases (GRKs), a family consisting of seven members (GRK 1–7), play a critical role.1 Endothelins (ETs) are a family of peptides comprising ET1, ET2, and ET3.2 ETs exert their actions through two types of receptors, ETA and ETB, which belong to the GPCR family.3 Activation of ETA receptors results in vasoconstriction through the generation of 1,4,5-inositol trisphosphate and diacylglycerol as intracellular messengers, which, in turn, trigger intracellular Ca2+ release and protein kinase C activation. Among the ET family members, ET1 is a potent vasoconstrictor that induces contraction at nanomolar concentrations in several vascular beds.3 Significant desensitization of ET1-induced cellular response was soon reported after ET was discovered in 1988,4 but the underlying mechanisms were not fully understood.
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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".