{"id":"e69a0b06-68ab-5cc0-9679-4fb13835fcf6","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-neutrophil-camp","predicate":"enhances_subsequent_agonist_response","statement":"After caffeine exposure, NECA stimulation produced greater cAMP accumulation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"1d83fac9-9e13-505a-90ff-fabdfccf1c37","mechanism_event_label":"The adapted cells responded more strongly to an adenosine agonist.","subject":{"id":"ef028472-7c33-583d-b52e-40676004d370","slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"},"object":{"id":"eea23cce-748c-5b69-819f-6802c5c38196","slug":"neutrophil-neca-camp-response","display_name":"Human neutrophil cAMP response to NECA","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"1d83fac9-9e13-505a-90ff-fabdfccf1c37","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-neutrophil-camp-event","event_type":"observed_relationship","label":"The adapted cells responded more strongly to an adenosine agonist.","description":"After caffeine exposure, NECA stimulation produced greater cAMP accumulation.","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":"eea23cce-748c-5b69-819f-6802c5c38196","slug":"neutrophil-neca-camp-response","display_name":"Human neutrophil cAMP response to NECA","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6bebe966-e8de-5a69-aa15-8e651fc58e10","slug":"adora2a","display_name":"Human adenosine A2A receptor / ADORA2A","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"459bd59a-6653-5920-880f-bd1b259349c0","slug":"neca","display_name":"5′-N-Ethylcarboxamidoadenosine / NECA","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"9cc3323e-3a7f-5be5-91ae-78dab284fb81","slug":"cyclic-amp","display_name":"Cyclic adenosine monophosphate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human neutrophils after 400 or 600 mg/day for one week, or 400 mg/day for two weeks; ex-vivo binding and NECA challenges.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Adapted cells were challenged with an agonist; this is not the same as an immediate effect of caffeine, nor a clinical anti-inflammatory trial.","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":"The adapted cells responded more strongly to an adenosine agonist.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Caffeine intake induces an alteration in human neutrophil A2A adenosine receptors. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16143823/ · DOI 10.1007/s00018-005-5312-z","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"16c75cec-600f-53c1-9917-9a8a7c2a9000","evidence_kind":"source_excerpt","locator":"Lines 156-162","start_line":156,"end_line":162,"excerpt":"## caf-neutrophil-camp\nThe adapted cells responded more strongly to an adenosine agonist.\nAfter caffeine exposure, NECA stimulation produced greater cAMP accumulation.\nModel: Human neutrophils after 400 or 600 mg/day for one week, or 400 mg/day for two weeks; ex-vivo binding and NECA challenges.\nLimitations: Adapted cells were challenged with an agonist; this is not the same as an immediate effect of caffeine, nor a clinical anti-inflammatory trial.\nEvidence access: Primary abstract\nCaffeine intake induces an alteration in human neutrophil A2A adenosine receptors. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16143823/ · DOI 10.1007/s00018-005-5312-z","model_system":"Human neutrophils after 400 or 600 mg/day for one week, or 400 mg/day for two weeks; ex-vivo binding and NECA challenges.","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. 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