Absence of ligand‐induced regulation of kinin receptor expression in the rabbit
Bibliographic record
Abstract
The induction of B(1) receptors (B(1)Rs) and desensitization or down-regulation of B(2) receptors (B(2)Rs) as a consequence of the production of endogenous kinins has been termed the autoregulation hypothesis. The latter was investigated using two models based on the rabbit: kinin stimulation of cultured vascular smooth muscle cells (SMCs) and in vivo contact system activation (dextran sulphate intravenous injection, 2 mg kg(-1), 5 h). Rabbit aortic SMCs express a baseline population of B(1)Rs that was up-regulated upon interleukin-1beta treatment ([(3)H]-Lys-des-Arg(9)-BK binding or mRNA concentration evaluated by RT - PCR; 4 or 3 h, respectively). Treatment with B(1)R or B(2)R agonists failed to alter B(1)R expression under the same conditions. Despite consuming endogenous kininogen (assessed using the kinetics of immunoreactive kinin formation in the plasma exposed to glass beads ex vivo) and producing hypotension mediated by B(2)Rs in anaesthetized rabbits, dextran sulphate treatment failed to induce B(1)Rs in conscious animals (RT - PCR in several organs, aortic contractility). By contrast, lipopolysaccharide (LPS, 50 microg kg(-1), 5 h) was an effective B(1)R inducer (kidney, duodenum, aorta) but did not reduce kininogen reserve. We tested the alternate hypothesis that endogenous kinin participate in LPS induction of B(1)Rs. Kinin receptor antagonists (icatibant combined to B-9858, 50 microg kg(-1) of each) failed to prevent or reduce the effect of LPS on B(1)R expression. Dextran sulphate or LPS treatments did not persistently down-regulate vascular B(2)Rs (jugular vein contractility assessed ex vivo). The kinin receptor autoregulation hypothesis is not applicable to primary cell cultures derived from a tissue known to express B(1)Rs in a regulated manner (aorta). The activation of the endogenous kallikrein-kinin system is ineffective to induce B(1)Rs in vivo in an experimental time frame sufficient for B(1)R induction by LPS.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".