Involvement of the cyclic GMP pathway in the superoxide-induced IP3 formation in vascular smooth muscle cells
Bibliographic record
Abstract
OBJECTIVE: To investigate whether cGMP or cAMP signal pathway is indirectly involved in the effect of superoxide on the IP3 formation in vascular smooth muscle cells (SMC) from rat mesenteric arteries. METHODS: Cultured smooth muscle cells from rat mesenteric arteries were prelabelled with myo-(2-(3)H) inositol for evaluation of IP3 formation. Quantitative cAMP and cGMP levels were determined using cAMP [3H] or cGMP [125I] assay systems. RESULTS: In the present study, it was found that superoxide significantly inhibited the basal level of cGMP and also suppressed the sodium nitroprusside (SNP)-induced cGMP formation in SMCs from rat mesenteric arteries. The inhibitory effect of superoxide on basal level of cGMP was similar in the absence or presence of ODQ (a guanylyl cyclase inhibitor). Moreover, the superoxide-induced increase in IP3 formation was significantly inhibited by SNP or s-nitroso- n-acetylpenicillamine but was significantly potentiated by ODQ or KT5823 (a cGMP-dependent protein kinase inhibitor). Superoxide had no effect on the basal or on the forskolin-induced cAMP production and the inhibition of adenylyl cyclase or cAMP-dependent protein kinase did not affect the superoxide-enhanced IP3 formation. CONCLUSION: The decreased cross-inhibition of IP3 pathway by cGMP may contribute to the superoxide-enhanced IP3 formation in SMCs from mesenteric arteries. The cross-talk between cGMP and IP3 pathways provides a novel mechanism for the signalling role of superoxide in vascular SMCs.
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".