Subcellular localization of PDE5 allows for select cGMP signaling in discrete microdomains in human aortic smooth muscle cells
Bibliographic record
Abstract
Cyclic GMP (cGMP) is a ubiquitous intracellular messenger that acts to integrate and translate the information encoded by extracellular messenger molecules including nitric oxide. Recently we demonstrated that specific localization of phosphodiesterase 5 (PDE5) allowed spatial and temporal regulation of cGMP signaling in platelets. Specifically, PDE5 was identified as an integral component of a Protein Kinase G (PKG) and an inositol‐1,4,5‐trisphosphate receptor (IP 3 R) signaling complex where it acts to selectively regulate IP 3 mediated Ca 2+ release. Subsequently, we have investigated the role of PDE5 in human aortic smooth muscle cells (HASMC). The presented findings demonstrate that HASMC contains two pools of PDE5. One pool of PDE5 is tethered in the same cGMP‐signaling complex consisting of PDE5, PKG and IP 3 R and is responsible for regulating IP 3 mediated Ca 2+ release. Interestingly, we provide evidence that the untethered PDE5 plays an essential role in regulating proliferation in these cells. Inhibition of PDE5 in HASMC increased DNA synthesis measured by ( 3 H) thymidine incorporation. Our findings provide insight into the role of specific pools of PDE5 in these cells and suggest that discrete domains of cGMP exist in HASMC. We suggest that by further elucidating the role of PDE5 we may define a molecular mechanism by which PDE5 inhibition can differentially impact selected cellular functions in these cells.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".