Platelet aggregation: molecular mechanisms & dependencies

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

Human evidence only

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What acts on it

In human platelet extracts PDE2, PDE3 and PDE5 were identified with no PDE1 or PDE4, cyclic GMP hydrolytic activity was about six times higher than cyclic AMP hydrolytic activity, platelets were among the tissues richest in PDE5, and the selective inhibitor E4021 up to 10 micromolar did not inhibit thromboxane-analogue-induced aggregation on its own while E4021 plus the nitric oxide donor SIN-1, at concentrations that had little effect individually, did inhibit aggregation.
E4021, a selective PDE5 inhibitor → Platelet aggregation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sildenafil-research/9115850.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff6132fc80fceda8601406e8827a621afbb66fb4ebaf2bcd4f722ac875c73a54", "start_char": 0, "end_char": 1152, "text_sha256": "ff6132fc80fceda8601406e8827a621afbb66fb4ebaf2bcd4f722ac875c73a54"}
experimental_model
Phosphodiesterase isoenzyme separation from human platelet extracts with aggregometry
exposure
A selective PDE5 inhibitor alone and combined with the nitric oxide donor SIN-1
limitations
Establishes the enzyme complement of the platelet and tests whether inhibiting it is sufficient. It uses E4021 rather than sildenafil, which is recorded on the claim.
nutrient_topic
Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil
organism
Human
plain_language
The tissue richest in this enzyme is unaffected by blocking it unless something is making the messenger.
primary_references
[sil-p9115850] Characterization of the isoenzymes of cyclic nucleotide phosphodiesterase in human platelets and the effects of E4021. (1996). https://pubmed.ncbi.nlm.nih.gov/9115850/ DOI: 10.1016/s0898-6568(96)00112-x
tissue_or_cell_type
Platelets
Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 340–351
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphodiesterase isoenzyme separation from human platelet extracts with aggregometry · source_derived_draft · unverified_draft
### sil-inhibition-alone-is-not-enough In human platelet extracts PDE2, PDE3 and PDE5 were identified with no PDE1 or PDE4, cyclic GMP hydrolytic activity was about six times higher than cyclic AMP hydrolytic activity, platelets were among the tissues richest in PDE5, and the selective inhibitor E4021 up to 10 micromolar did not inhibit thromboxane-analogue-induced aggregation on its own while E4021 plus the nitric oxide donor SIN-1, at concentrations that had little effect individually, did inhibit aggregation. Condition category: normal nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: The tissue richest in this enzyme is unaffected by blocking it unless something is making the messenger. organism: Human tissue_or_cell_type: Platelets experimental_model: Phosphodiesterase isoenzyme separation from human platelet extracts with aggregometry limitations: Establishes the enzyme complement of the platelet and tests whether inhibiting it is sufficient. It uses E4021 rather than sildenafil, which is recorded on the claim. exposure: A selective PDE5 inhibitor alone and combined with the nitric oxide donor SIN-1 evidence_span: {"source_cache": "artifacts/sildenafil-research/9115850.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff6132fc80fceda8601406e8827a621afbb66fb4ebaf2bcd4f722ac875c73a54", "start_char": 0, "end_char": 1152, "text_sha256": "ff6132fc80fceda8601406e8827a621afbb66fb4ebaf2bcd4f722ac875c73a54"} [sil-p9115850] Characterization of the isoenzymes of cyclic nucleotide phosphodiesterase in human platelets and the effects of E4021. (1996). https://pubmed.ncbi.nlm.nih.gov/9115850/ DOI: 10.1016/s0898-6568(96)00112-x
Complete structured claim and evidence
Human platelets were found to contain PDE5 which was inhibited by sildenafil with a half-maximal inhibitory concentration of 6.3 nanomolar consistent with the value in corpus cavernosum, sildenafil alone had no direct effect on platelet function but it potentiated the in vitro antiaggregatory activity of sodium nitroprusside on rabbit and human platelets, and in phenylephrine-contracted rabbit aortic rings it enhanced glyceryl trinitrate relaxation.
Sildenafil → Platelet aggregation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sildenafil-research/10078537.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dceb60af4400fe67b4ffaf73a0aadb8d2e5fad0966b3372a3e46a91c0e0ccee5", "start_char": 0, "end_char": 2610, "text_sha256": "dceb60af4400fe67b4ffaf73a0aadb8d2e5fad0966b3372a3e46a91c0e0ccee5"}
experimental_model
Immunochemical distribution of phosphodiesterase activity across human tissues with isolated organ bath studies and platelet aggregometry
exposure
Anti-PDE1 and anti-PDE5 antibodies with functional testing, and sildenafil against sodium nitroprusside on platelets
limitations
Maps where the target enzyme is and is not, which is what predicts where the drug acts. Antibody-based detection, so absence of signal is weaker evidence than presence.
nutrient_topic
Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil
organism
Human, rabbit and dog
plain_language
Platelets carry the same enzyme, and again the drug does nothing to them until a nitric oxide donor is present.
primary_references
[sil-p10078537] Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. (1999). https://pubmed.ncbi.nlm.nih.gov/10078537/ DOI: 10.1016/s0002-9149(99)00042-9
tissue_or_cell_type
Cardiac ventricle, saphenous vein, mesenteric artery, corpus cavernosum and platelets
Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 327–338
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immunochemical distribution of phosphodiesterase activity across human tissues with isolated organ bath studies and platelet aggregometry · source_derived_draft · unverified_draft
### sil-platelets-need-a-donor-too Human platelets were found to contain PDE5 which was inhibited by sildenafil with a half-maximal inhibitory concentration of 6.3 nanomolar consistent with the value in corpus cavernosum, sildenafil alone had no direct effect on platelet function but it potentiated the in vitro antiaggregatory activity of sodium nitroprusside on rabbit and human platelets, and in phenylephrine-contracted rabbit aortic rings it enhanced glyceryl trinitrate relaxation. Condition category: normal nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: Platelets carry the same enzyme, and again the drug does nothing to them until a nitric oxide donor is present. organism: Human, rabbit and dog tissue_or_cell_type: Cardiac ventricle, saphenous vein, mesenteric artery, corpus cavernosum and platelets experimental_model: Immunochemical distribution of phosphodiesterase activity across human tissues with isolated organ bath studies and platelet aggregometry limitations: Maps where the target enzyme is and is not, which is what predicts where the drug acts. Antibody-based detection, so absence of signal is weaker evidence than presence. exposure: Anti-PDE1 and anti-PDE5 antibodies with functional testing, and sildenafil against sodium nitroprusside on platelets evidence_span: {"source_cache": "artifacts/sildenafil-research/10078537.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dceb60af4400fe67b4ffaf73a0aadb8d2e5fad0966b3372a3e46a91c0e0ccee5", "start_char": 0, "end_char": 2610, "text_sha256": "dceb60af4400fe67b4ffaf73a0aadb8d2e5fad0966b3372a3e46a91c0e0ccee5"} [sil-p10078537] Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. (1999). https://pubmed.ncbi.nlm.nih.gov/10078537/ DOI: 10.1016/s0002-9149(99)00042-9
Complete structured claim and evidence

The events it takes part in

A mechanism often involves more than two components. These are the full events, with every participant and its role.

Situations it appears in

Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

Open hypotheses

Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.

This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

Platelet aggregation