{"id":"9eff3759-4f33-5021-9927-184df21342ab","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:nia-clin-hcar2-camp","predicate":"activation_lowers","statement":"Nicotinic-acid activation of GPR109A/HCAR2 in the human cell-line assay lowered cAMP through a pertussis-toxin-sensitive pathway.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"5746cb8c-2392-5a4b-912b-5baefa2f3195","mechanism_event_label":"Nicotinic acid can act as a receptor signal as well as a vitamin precursor, switching down a cellular signaling molecule.","subject":{"id":"c31b5501-5abf-57bb-8324-15923ed678cf","slug":"hcar2","display_name":"Human hydroxycarboxylic acid receptor 2 / HCAR2","entity_type_key":"protein"},"object":{"id":"ad0ccd02-b864-5373-b21e-85aa6d912f73","slug":"intracellular-camp-content","display_name":"Intracellular cyclic AMP content","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"5746cb8c-2392-5a4b-912b-5baefa2f3195","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:nia-clin-hcar2-camp-event","event_type":"biochemical_relationship","label":"Nicotinic acid can act as a receptor signal as well as a vitamin precursor, switching down a cellular signaling molecule.","description":"Nicotinic-acid activation of GPR109A/HCAR2 in the human cell-line assay lowered cAMP through a pertussis-toxin-sensitive pathway.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9751fdb6-9b30-586f-b07a-79b8e2cd62dd","slug":"nicotinic-acid","display_name":"Nicotinic acid","entity_type_key":"small_molecule"},"role":"agonist","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9cc3323e-3a7f-5be5-91ae-78dab284fb81","slug":"cyclic-amp","display_name":"Cyclic adenosine monophosphate","entity_type_key":"small_molecule"},"role":"measured_signal","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c31b5501-5abf-57bb-8324-15923ed678cf","slug":"hcar2","display_name":"Human hydroxycarboxylic acid receptor 2 / HCAR2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ad0ccd02-b864-5373-b21e-85aa6d912f73","slug":"intracellular-camp-content","display_name":"Intracellular cyclic AMP content","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Nicotinic acid (agonist); Cyclic adenosine monophosphate (measured_signal)","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/niacin-clinical-sources/walters2009.abstract.txt\", \"locator\": \"Indexed primary abstract\", \"file_sha256\": \"2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b\", \"start_char\": 0, \"end_char\": 1537, \"text_sha256\": \"2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human cell-line nicotinic-acid receptor signaling assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Nicotinic-acid stimulation and beta-arrestin perturbation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Niacin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"niacin","display_name":"Niacin (vitamin B3)","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Nicotinic acid can act as a receptor signal as well as a vitamin precursor, switching down a cellular signaling molecule.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cultured human cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"47f6a880-a517-58f1-947f-bb8844e90d1f","evidence_kind":"source_excerpt","locator":"Lines 1291-1303","start_line":1291,"end_line":1303,"excerpt":"### nia-clin-hcar2-camp\nNicotinic-acid activation of GPR109A/HCAR2 in the human cell-line assay lowered cAMP through a pertussis-toxin-sensitive pathway.\nCondition category: normal\nnutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Nicotinic acid can act as a receptor signal as well as a vitamin precursor, switching down a cellular signaling molecule.\norganism: Homo sapiens\ntissue_or_cell_type: Cultured human cells\nexperimental_model: Human cell-line nicotinic-acid receptor signaling assay\nlimitations: Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit.\nexposure: Nicotinic-acid stimulation and beta-arrestin perturbation\ncross_nutrient: Nicotinic acid (agonist); Cyclic adenosine monophosphate (measured_signal)\nevidence_span: {\"source_cache\": \"artifacts/niacin-clinical-sources/walters2009.abstract.txt\", \"locator\": \"Indexed primary abstract\", \"file_sha256\": \"2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b\", \"start_char\": 0, \"end_char\": 1537, \"text_sha256\": \"2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b\"}\n[nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806","model_system":"Human cell-line nicotinic-acid receptor signaling assay","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"a62b7b5b-786a-57e9-85e9-67c6912a5054","stable_key":"import-a9dd23c6-978a-5755-8bd8-f29bd1fe0cda","title":"Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"a8cac59639322f74812ce12eef338c2f6c385c04cc4af6ab511fc7c972f0c2e6","revision_id":"bec8fc45-12e7-5f75-a814-5d72ed015d01","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}