Isovaline Does Not Activate GABAB Receptor-Coupled Potassium Currents in GABAB Expressing AtT-20 Cells and Cultured Rat Hippocampal Neurons
Bibliographic record
Abstract
Isovaline is a non-proteinogenic amino acid that has analgesic properties. R-isovaline is a proposed agonist of the γ-aminobutyric acid type B (GABA(B)) receptor in the thalamus and peripheral tissue. Interestingly, the responses to R-isovaline differ from those of the canonical GABA(B) receptor agonist R-baclofen, warranting further investigation. Using whole cell recording techniques we explored isovaline actions on GABA(B) receptors coupled to rectifying K+ channels in cells of recombinant and native receptor preparations. In AtT-20 cells transfected with GABA(B) receptor subunits, bath application of the GABA(B) receptor agonists, GABA (1 μM) and R-baclofen (5 μM) produced inwardly rectifying currents that reversed approximately at the calculated reversal potential for K+ R- isovaline (50 μM to 1 mM) and S-isovaline (500 μM) did not evoke a current. R-isovaline applied either extracellularly (250 μM) or intracellularly (10 μM) did not alter responses to GABA at 1 μM. Co-administration of R-isovaline (250 μM) with a low concentration (10 nM) of GABA did not result in a response. In cultured rat hippocampal neurons that natively express GABA(B) receptors, R-baclofen (5 μM) induced GABA(B) receptor-dependent inward currents. Under the same conditions R-isovaline (1 or 50 μM) did not evoke a current or significantly alter R-baclofen-induced effects. Therefore, R-isovaline does not interact with recombinant or native GABA(B) receptors to open K+ channels in these preparations.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 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".