Renal Collecting Duct GSK3ß Deletion Affects Response To AVP By Reducing Adenylate Cyclase Activity
Bibliographic record
Abstract
Glycogen synthase kinase 3 (GSK3) is potently inhibited by lithium, a common treatment for bipolar disorders, which impairs urinary concentrating ability in 20‐30% of patients. To examine if GSK3ß is crucial for regulating vasopressin (AVP) dependent water reabsorption in the renal collecting duct (CD), we developed CD specific GSK3ß knockout mice (GSK3ß‐CD null). These mice had lower urine osmolality, renal aquaporin 2 (AQP2) mRNA and protein levels following water deprivation or dDAVP treatment, compared to wild type (WT) mice. dDAVP and forskolin induced cAMP generation was lower in the GSK3ß‐CD null mice and GSK3ß inhibitor treated WT mice or IMCD cells. We measured the renal AC activity in membrane preparation from WT and GSK3ß ‐CD null mice. dDAVP or forskolin induced AC activity in GSK3ß‐CD null group was reduced by up to 50% and 40% respectively compared to the WT group. Over 68% suppression of AC activity was observed in WT membranes treated with SB216763. These studies show for the first time that GSK3ß inhibition or deletion leads to lower cAMP generation due to reduced AC activity, which could be responsible for low AQP2 expression and impaired response to AVP in the GSK3ß‐CD null mice.
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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) | 0.000 | 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) | 0.004 | 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".