The 5TM VPAC1 Isoform Blocks cAMP Signaling Evoked from the Full‐Length 7TM receptor
Bibliographic record
Abstract
Vasoactive intestinal peptide receptor 1 (VPAC1) couples heterotrimeric G proteins, Gαs and Gαi, that activate and inhibit adenylate cyclase cAMP production. The 7 transmembrane (TM) VPAC1 isoform, increases intracellular cAMP ([cAMP]i) upon binding its ligand, vasoactive intestinal peptide (VIP). In contrast, the 5TM VPAC1 isoform fails to increase [cAMP]i over a range of 10‐6‐10‐12 M VIP. Our hypothesis is that the dual expression of both the 5 and 7TM isoforms cause a lack of [cAMP]i elevation due to an antagonist effect by the 5TM on 7TM signaling. To investigate this, human HuT 78 cells, a malignant T cell, which express both 5 and 7TM VPAC1 isoforms. Levels of [cAMP]i were measured by a competitive ELISA after treating with increasing concentrations of VIP. Interesting, we show a VIP dependent decrease in [cAMP]i, suggesting that the 5TM VPAC1 isoform coexpressed in HuT 78 cells suppress 7 TM induced [cAMP]i levels. The ratio of the 5 and 7TM receptors on the cell membrane may explain the unique level of [cAMP]i upon VIP binding. Future studies will inhibit Gαi coupling with pertussis toxin and RNAi to knockdown the 5TM VPAC1 to measure [cAMP]i response evoked by the 7TM VPAC‐1 receptor in coexpressing cells. Research supported by NIH‐KO1 1KO1DK664828 and COBRE 2P20RR015566.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".