Component
Human corpus cavernosum trabecular smooth muscle
Human corpus cavernosum trabecular smooth muscle. Species, exposure and limitations are retained in each linked claim.
3 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
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.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
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.
What acts on it
Both cyclic GMP and cyclic AMP specific phosphodiesterases were identified in human corpora cavernosa in vitro, the main phosphodiesterase activity in this tissue being due to PDE5 with PDE2 and PDE3 also identified, and sildenafil is a selective inhibitor of PDE5 with a mean half-maximal inhibitory concentration of 0.0039 micromolar.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/sildenafil-research/8858389.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "173f69debd8427b8a1c001e543e4356f2d3b90c730ca3217073a25c4bc61905a", "start_char": 0, "end_char": 1288, "text_sha256": "173f69debd8427b8a1c001e543e4356f2d3b90c730ca3217073a25c4bc61905a"}
- experimental_model
- Phosphodiesterase isozyme characterisation in human corpora cavernosa with volunteer pharmacokinetics and a small clinical study
- exposure
- Sildenafil assayed against phosphodiesterase isozymes prepared from human tissue
- limitations
- The first report of the compound. The clinical arm is twelve patients without an established organic cause, so it establishes the target rather than the treatment effect.
- 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
- One of the several enzymes in this tissue carries most of the activity, and the drug was built against that one.
- primary_references
- [sil-p8858389] Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. (1996). https://pubmed.ncbi.nlm.nih.gov/8858389/
- tissue_or_cell_type
- Corpus cavernosum
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphodiesterase isozyme characterisation in human corpora cavernosa with volunteer pharmacokinetics and a small clinical study · source_derived_draft · unverified_draft
### sil-pde5-is-the-main-isozyme Both cyclic GMP and cyclic AMP specific phosphodiesterases were identified in human corpora cavernosa in vitro, the main phosphodiesterase activity in this tissue being due to PDE5 with PDE2 and PDE3 also identified, and sildenafil is a selective inhibitor of PDE5 with a mean half-maximal inhibitory concentration of 0.0039 micromolar. 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: One of the several enzymes in this tissue carries most of the activity, and the drug was built against that one. organism: Human tissue_or_cell_type: Corpus cavernosum experimental_model: Phosphodiesterase isozyme characterisation in human corpora cavernosa with volunteer pharmacokinetics and a small clinical study limitations: The first report of the compound. The clinical arm is twelve patients without an established organic cause, so it establishes the target rather than the treatment effect. exposure: Sildenafil assayed against phosphodiesterase isozymes prepared from human tissue evidence_span: {"source_cache": "artifacts/sildenafil-research/8858389.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "173f69debd8427b8a1c001e543e4356f2d3b90c730ca3217073a25c4bc61905a", "start_char": 0, "end_char": 1288, "text_sha256": "173f69debd8427b8a1c001e543e4356f2d3b90c730ca3217073a25c4bc61905a"} [sil-p8858389] Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. (1996). https://pubmed.ncbi.nlm.nih.gov/8858389/
Complete structured claim and evidence
Where it participates (unsigned role)
Sildenafil at 0.001 to 1 micromolar enhanced the electrical-field-stimulation-induced, nitric-oxide-dependent relaxation of human corpus cavernosum in a concentration-dependent manner to a maximum of three times the pretreatment level at 1 micromolar, supporting the proposal that the drug acts by potentiating the nitric-oxide-stimulated cyclic GMP signal mediating relaxation of cavernosal smooth muscle during sexual stimulation.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/sildenafil-research/9598563.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "860e09237bbae4ec5bb65a640186902908ccb9c6ec502b504a1ecddbb33810a2", "start_char": 0, "end_char": 1755, "text_sha256": "860e09237bbae4ec5bb65a640186902908ccb9c6ec502b504a1ecddbb33810a2"}
- experimental_model
- Isolated human corpus cavernosum strips with electrical field stimulation, and phosphodiesterase assays across families 1 to 6
- exposure
- Sildenafil against PDE1 to PDE5 prepared from human tissues and PDE6 from bovine retina, with zaprinast as comparator
- limitations
- Measures the full selectivity series in one laboratory using the same method, which is what makes the ratios comparable. The PDE6 preparation is bovine retina rather than human.
- 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 and bovine enzyme
- plain_language
- It triples a relaxation the nerves were already producing; it does not produce one of its own.
- primary_references
- [sil-p9598563] Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. (1998). https://pubmed.ncbi.nlm.nih.gov/9598563/ DOI: 10.1016/s0022-5347(01)63299-3
- tissue_or_cell_type
- Corpus cavernosum and bovine retina
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated human corpus cavernosum strips with electrical field stimulation, and phosphodiesterase assays across families 1 to 6 · source_derived_draft · unverified_draft
### sil-amplifies-nitrergic-relaxation Sildenafil at 0.001 to 1 micromolar enhanced the electrical-field-stimulation-induced, nitric-oxide-dependent relaxation of human corpus cavernosum in a concentration-dependent manner to a maximum of three times the pretreatment level at 1 micromolar, supporting the proposal that the drug acts by potentiating the nitric-oxide-stimulated cyclic GMP signal mediating relaxation of cavernosal smooth muscle during sexual stimulation. 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: It triples a relaxation the nerves were already producing; it does not produce one of its own. organism: Human and bovine enzyme tissue_or_cell_type: Corpus cavernosum and bovine retina experimental_model: Isolated human corpus cavernosum strips with electrical field stimulation, and phosphodiesterase assays across families 1 to 6 limitations: Measures the full selectivity series in one laboratory using the same method, which is what makes the ratios comparable. The PDE6 preparation is bovine retina rather than human. exposure: Sildenafil against PDE1 to PDE5 prepared from human tissues and PDE6 from bovine retina, with zaprinast as comparator evidence_span: {"source_cache": "artifacts/sildenafil-research/9598563.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "860e09237bbae4ec5bb65a640186902908ccb9c6ec502b504a1ecddbb33810a2", "start_char": 0, "end_char": 1755, "text_sha256": "860e09237bbae4ec5bb65a640186902908ccb9c6ec502b504a1ecddbb33810a2"} [sil-p9598563] Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. (1998). https://pubmed.ncbi.nlm.nih.gov/9598563/ DOI: 10.1016/s0022-5347(01)63299-3
Complete structured claim and evidenceIn the concentration range 0.01 to 1 micromolar there was only a minor effect of sildenafil on cyclic GMP levels in isolated human cavernous and cardiac tissues, whereas sildenafil significantly increased cyclic AMP in both at physiologic and supraphysiologic concentrations, more pronounced in cavernous than cardiac tissue, and in the range 0.1 to 1.0 micromolar the effect on cyclic AMP in cardiac samples was almost equivalent to that of milrinone, which the authors offer as a potential mechanism for reported cardiovascular effects and as evidence of cross-talk between the two signalling pathways.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/sildenafil-research/10654914.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "95ba66c3ea65d0610adf58e7ab0bca314da8353ecac3f86272c780678929d292", "start_char": 0, "end_char": 1867, "text_sha256": "95ba66c3ea65d0610adf58e7ab0bca314da8353ecac3f86272c780678929d292"}
- experimental_model
- Radioimmunoassay of cyclic nucleotide accumulation in isolated human corpus cavernosum and cardiac muscle
- exposure
- Sildenafil from 0.01 to 1 micromolar against sodium nitroprusside, forskolin and milrinone as reference compounds
- limitations
- Measures both cyclic nucleotides in human tissue with reference compounds for each pathway, and reports an effect on the nucleotide the drug is not supposed to touch. It is an isolated tissue study without added nitric oxide drive.
- 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
- In this tissue the drug barely moved the messenger it targets and raised the other one instead.
- primary_references
- [sil-p10654914] Effects of sildenafil on cAMP and cGMP levels in isolated human cavernous and cardiac tissue. (2000). https://pubmed.ncbi.nlm.nih.gov/10654914/ DOI: 10.1016/s0090-4295(99)00371-4
- tissue_or_cell_type
- Corpus cavernosum and cardiac muscle
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radioimmunoassay of cyclic nucleotide accumulation in isolated human corpus cavernosum and cardiac muscle · source_derived_draft · unverified_draft
### sil-cyclic-amp-rose-instead In the concentration range 0.01 to 1 micromolar there was only a minor effect of sildenafil on cyclic GMP levels in isolated human cavernous and cardiac tissues, whereas sildenafil significantly increased cyclic AMP in both at physiologic and supraphysiologic concentrations, more pronounced in cavernous than cardiac tissue, and in the range 0.1 to 1.0 micromolar the effect on cyclic AMP in cardiac samples was almost equivalent to that of milrinone, which the authors offer as a potential mechanism for reported cardiovascular effects and as evidence of cross-talk between the two signalling pathways. 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: In this tissue the drug barely moved the messenger it targets and raised the other one instead. organism: Human tissue_or_cell_type: Corpus cavernosum and cardiac muscle experimental_model: Radioimmunoassay of cyclic nucleotide accumulation in isolated human corpus cavernosum and cardiac muscle limitations: Measures both cyclic nucleotides in human tissue with reference compounds for each pathway, and reports an effect on the nucleotide the drug is not supposed to touch. It is an isolated tissue study without added nitric oxide drive. exposure: Sildenafil from 0.01 to 1 micromolar against sodium nitroprusside, forskolin and milrinone as reference compounds evidence_span: {"source_cache": "artifacts/sildenafil-research/10654914.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "95ba66c3ea65d0610adf58e7ab0bca314da8353ecac3f86272c780678929d292", "start_char": 0, "end_char": 1867, "text_sha256": "95ba66c3ea65d0610adf58e7ab0bca314da8353ecac3f86272c780678929d292"} [sil-p10654914] Effects of sildenafil on cAMP and cGMP levels in isolated human cavernous and cardiac tissue. (2000). https://pubmed.ncbi.nlm.nih.gov/10654914/ DOI: 10.1016/s0090-4295(99)00371-4
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.