Blockade of neuropeptide Y<sub>2</sub> receptors and suppression of NPY's anti‐epileptic actions in the rat hippocampal slice by BIIE0246
Bibliographic record
Abstract
Neuropeptide Y (NPY) has been shown to suppress synaptic excitation in rat hippocampus by a presynaptic action. The Y(2) (Y(2)R) and the Y(5) (Y(5)R) receptors have both been implicated in this action. We used the non-peptide, Y(2)R-selective antagonist, BIIE0246, to test the hypothesis that the Y(2)R mediates both the presynaptic inhibitory and anti-epileptic actions of NPY in rat hippocampus in vitro. NPY and the Y(2)R-selective agonist, [ahx(5-24)]NPY, both inhibited the population excitatory postsynaptic potential (pEPSP) evoked in area CA1 by stratum radiatum stimulation in a concentration-dependent manner. BIIE0246 suppressed the inhibitory effects of both agonists, suppressing the maximal inhibition without causing a change in the agonist EC(50), in a manner inconsistent with competitive antagonism. BIIE0246 washed out from hippocampal slices extremely slowly. Application of agonist at high concentrations (1 - 3 microM) for prolonged periods did not alter the rate of washout, but did partially overcome the antagonism, inconsistent with an insurmountable antagonism by BIIE0246. In the stimulus train-induced bursting (STIB) model of ictal activity in hippocampal slices, both NPY and [ahx(5-24)]NPY inhibited primary afterdischarge (1 degrees AD) activity. BIIE0246 (100 nM) completely suppressed the actions of NPY and [ahx(5-24)]NPY in this model. In contrast, the potent Y(5)R-selective agonist, Ala(31)Aib(32)NPY, affected neither 1 degrees AD activity in the presence of BIIE0246, nor, by itself, even the pEPSP in CA1. BIIE0246 potently suppresses NPY actions in rat hippocampus, suggesting a dominant role for Y(2)R there. The apparently insurmountable antagonism observed may result from the lipophilic nature of the antagonist.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".