{"id":"3ad066a1-6f4e-5563-9063-b0228ef0b2c2","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-ryr","predicate":"activates","statement":"Millimolar caffeine activated the skeletal-muscle ryanodine-receptor system; xanthine substitution altered ryanodine binding.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"84bd4370-dfbe-586d-aef8-0ee1a9ec0cda","mechanism_event_label":"At high experimental concentrations caffeine affects calcium-release machinery.","subject":{"id":"ef028472-7c33-583d-b52e-40676004d370","slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"},"object":{"id":"beeae430-fb17-554a-bed4-8eb5ca679f35","slug":"rabbit-ryr1","display_name":"Rabbit skeletal-muscle ryanodine receptor 1 / Ryr1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"84bd4370-dfbe-586d-aef8-0ee1a9ec0cda","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-ryr-event","event_type":"observed_relationship","label":"At high experimental concentrations caffeine affects calcium-release machinery.","description":"Millimolar caffeine activated the skeletal-muscle ryanodine-receptor system; xanthine substitution altered ryanodine binding.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ef028472-7c33-583d-b52e-40676004d370","slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"beeae430-fb17-554a-bed4-8eb5ca679f35","slug":"rabbit-ryr1","display_name":"Rabbit skeletal-muscle ryanodine receptor 1 / Ryr1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ac600753-3415-5856-8766-724960198ac3","slug":"skeletal-muscle-calcium-release","display_name":"Skeletal-muscle sarcoplasmic-reticulum calcium release","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rabbit skeletal-muscle sarcoplasmic-reticulum vesicles; structure–activity comparison.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Millimolar preparation effects must not be presented as the mechanism of every ordinary caffeinated drink.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Caffeine collection; salts, coffee, species and coexposure contexts retain their identities.","comparator":null,"unit":null,"notes":"","entity":{"slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"At high experimental concentrations caffeine affects calcium-release machinery.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Structure-activity relationship of xanthines and skeletal muscle ryanodine receptor/Ca2+ release channel. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9127436/ · DOI 10.1159/000139480","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"6e61095f-3e9c-565a-86dc-9cda0f9d693c","evidence_kind":"source_excerpt","locator":"Lines 380-386","start_line":380,"end_line":386,"excerpt":"## caf-ryr\nAt high experimental concentrations caffeine affects calcium-release machinery.\nMillimolar caffeine activated the skeletal-muscle ryanodine-receptor system; xanthine substitution altered ryanodine binding.\nModel: Rabbit skeletal-muscle sarcoplasmic-reticulum vesicles; structure–activity comparison.\nLimitations: Millimolar preparation effects must not be presented as the mechanism of every ordinary caffeinated drink.\nEvidence access: Primary abstract\nStructure-activity relationship of xanthines and skeletal muscle ryanodine receptor/Ca2+ release channel. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9127436/ · DOI 10.1159/000139480","model_system":"Rabbit skeletal-muscle sarcoplasmic-reticulum vesicles; structure–activity comparison.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access stated with the claim.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"40a654db-878c-5471-bc6c-88f4f52599c0","stable_key":"import-ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6","title":"Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"780d73d4abd45a0284d2cc0c646dbe8432ae347362891a4b98a19a61341a7325","revision_id":"f36ffb0a-d6df-522f-b783-5e30214b9e26","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}