Autoradiographic distribution and alterations of kinin B2 receptors in the brain and spinal cord of streptozotocin-diabetic rats
Bibliographic record
Abstract
This study investigates whether bradykinin (BK) B(2) receptor binding sites are increased in the brain and thoracic spinal cord of streptozotocin (STZ)-diabetic rats at 2, 7, and 21 days posttreatment by in vitro autoradiography with the radioligand [(125)I]HPP-Hoe 140. In control and diabetic rats, specific binding sites for B(2) receptors were detected in the brain and in various laminae of the spinal cord, predominantly in superficial laminae (K(d)=34 pM). In diabetic rats, B(2) receptor densities were significantly increased in lamina l of the dorsal horn (+35% at 7 and 21 days), spinal trigeminal nucleus (+70% at 7 and 21 days) and nucleus tractus solitarius (+100% at 2 and 7 days). B(2) receptor analogues D-Arg[Hyp(3),Thi(5),D-Tic(7),Oic(8)]-BK (Hoe 140), 3-(4 hydroxyphenyl)propionyl-Hoe 140 (HPP-Hoe 140), LF16-0687 mesylate ((2-Pyrrolidinecarboxamide, N-[3-[[4-aminoiminomethyl)benzoyl]amino]propyl]-1-[[2,4-dichoro-3-[[(2,4-dimethyl-8-quinolinyl)oxy]methyl]phenyl]sulfonyl]-(2S)-(9Cl)), and BK decreased binding of [(125)I]-HPP-Hoe 140 in the spinal dorsal horn, with K(i) values of 0.5, 1.5, 3.2, and 3.7 nM, respectively. These values were not significantly different in diabetic rats at 7 days (0.5 (Hoe 140), 0.7 (HPP-Hoe 140), 1.2 (BK), and 1.7 (LF16-0687) nM). While des-Arg(10)-Hoe 140 was three orders of magnitude less potent than Hoe 140, B(1) receptor agonist (des-Arg(9)-BK) and antagonist (AcLys[D-betaNal(7),Ile(8)]des-Arg(9)-BK, R-715) did not affect [(125)I]-HPP-Hoe 140 binding at 1 microM concentration. Data suggest a very discrete and temporal increase of B(2) receptor density (without affinity changes) in the spinal cord and hindbrain of STZ-diabetic rats. This contrasts with the early induction and over-expression of B(1) receptors reported in the brain and spinal cord of STZ-diabetic rats.
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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 | 0.001 | 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) | 0.002 | 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".