{"id":"e67588ea-69fe-5e55-afee-00f23b56b7c5","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-kyna-alpha7-rat-null","predicate":"does_not_inhibit_in_report","statement":"Kynurenic acid did not inhibit choline-evoked alpha7 currents in rat hippocampal slice interneurons, contrasting with earlier reports.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"d6760e31-7a44-5a02-ad46-3fcbf673bd19","mechanism_event_label":"Another experiment did not reproduce the claimed receptor block.","subject":{"id":"6a123629-5a43-57ef-bba0-c429005ab5b3","slug":"kynurenic-acid","display_name":"Kynurenic acid","entity_type_key":"small_molecule"},"object":{"id":"32fd2639-0ba4-537f-a4a8-95b27981f6c2","slug":"rat-chrna7-receptors","display_name":"Rat alpha7-containing nicotinic acetylcholine receptors","entity_type_key":"protein_complex"},"evidence_count":1,"mechanism_event":{"id":"d6760e31-7a44-5a02-ad46-3fcbf673bd19","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-kyna-alpha7-rat-null-event","event_type":"observed_relationship","label":"Another experiment did not reproduce the claimed receptor block.","description":"Kynurenic acid did not inhibit choline-evoked alpha7 currents in rat hippocampal slice interneurons, contrasting with earlier reports.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6a123629-5a43-57ef-bba0-c429005ab5b3","slug":"kynurenic-acid","display_name":"Kynurenic acid","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"32fd2639-0ba4-537f-a4a8-95b27981f6c2","slug":"rat-chrna7-receptors","display_name":"Rat alpha7-containing nicotinic acetylcholine receptors","entity_type_key":"protein_complex"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"769339cb-213b-559e-acc0-07ed00368b94","slug":"l-tryptophan","display_name":"L-Tryptophan","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"8e1d19fd-ad66-575d-81c4-9122f78915e5","slug":"choline","display_name":"Choline","entity_type_key":"small_molecule"},"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":"Adolescent rat stratum-radiatum interneurons in acute slices.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Slice age, temperature, agonist delivery and receptor environment are candidate explanations, not a demonstrated resolution.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-tryptophan","display_name":"L-Tryptophan","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Another experiment did not reproduce the claimed receptor block.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Lack of modulation of nicotinic acetylcholine alpha-7 receptor currents by kynurenic acid in adult hippocampal interneurons. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22848433/ · DOI 10.1371/journal.pone.0041108","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2685be2a-424e-506f-856a-a53a0ab084d8","evidence_kind":"source_excerpt","locator":"Lines 298-304","start_line":298,"end_line":304,"excerpt":"## tryptophan-kyna-alpha7-rat-null\nAnother experiment did not reproduce the claimed receptor block.\nKynurenic acid did not inhibit choline-evoked alpha7 currents in rat hippocampal slice interneurons, contrasting with earlier reports.\nModel: Adolescent rat stratum-radiatum interneurons in acute slices.\nLimitations: Slice age, temperature, agonist delivery and receptor environment are candidate explanations, not a demonstrated resolution.\nEvidence access: Primary abstract\nLack of modulation of nicotinic acetylcholine alpha-7 receptor currents by kynurenic acid in adult hippocampal interneurons. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22848433/ · DOI 10.1371/journal.pone.0041108","model_system":"Adolescent rat stratum-radiatum interneurons in acute slices.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"73f9d3e7-fdc9-5418-8f3c-f4ef145f6efa","stable_key":"import-584c58f5-ab9f-53f3-97a9-55783db943b0","title":"Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19)","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":"7dfd20063b91900cb5c6ad675e3e675b7e25ef0fb8304eabac6f263cc5518284","revision_id":"bfafd789-fdf5-521f-bd28-c662e01ec1ea","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"ffd27f79-008d-5738-9d8d-1ceb13b98647","title":"Does kynurenic acid directly inhibit alpha7 nicotinic receptors?","kind":"contradiction","status":"open","why":"A 2001 neuronal study reported inhibition, whereas a 2012 rat/mouse slice study found no alpha7-current inhibition despite effective glutamatergic blockade and prolonged high exposure. This is an experimental disagreement, not a correction of draft wording.","resolution":"Retain both findings. Culture versus acute slice, developmental stage, temperature, agonist delivery and receptor environment may matter, but no candidate explanation is treated here as proven. Do not represent alpha7 antagonism as a universal established action of kynurenic acid.","created_at":"2026-09-19 06:25:16","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/ffd27f79-008d-5738-9d8d-1ceb13b98647","sides":[{"conflict_id":"ffd27f79-008d-5738-9d8d-1ceb13b98647","ordinal":0,"label":"Reported inhibition in rat neurons","revision_id":"bfafd789-fdf5-521f-bd28-c662e01ec1ea","start_line":290,"end_line":296,"quote":"## tryptophan-kyna-alpha7-positive\nOne laboratory reported suppression of an acetylcholine receptor.\nKynurenic acid inhibited alpha7 nicotinic responses in cultured rat hippocampal neurons after at least four minutes, with an IC50 near 7 micromolar.\nModel: Rat hippocampal culture and slice electrophysiology.\nLimitations: Direct alpha7 inhibition is disputed by a later slice study; retain assay context rather than treating it as universal.\nEvidence access: Primary abstract\nThe brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11567036/ · DOI 10.1523/JNEUROSCI.21-19-07463.2001","source_key":"import-584c58f5-ab9f-53f3-97a9-55783db943b0","source_title":"Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19)","claim_ids":["37d784f4-1c28-5d40-8d6f-a61a1d78dc28"]},{"conflict_id":"ffd27f79-008d-5738-9d8d-1ceb13b98647","ordinal":1,"label":"No inhibition in rat slice interneurons","revision_id":"bfafd789-fdf5-521f-bd28-c662e01ec1ea","start_line":298,"end_line":304,"quote":"## tryptophan-kyna-alpha7-rat-null\nAnother experiment did not reproduce the claimed receptor block.\nKynurenic acid did not inhibit choline-evoked alpha7 currents in rat hippocampal slice interneurons, contrasting with earlier reports.\nModel: Adolescent rat stratum-radiatum interneurons in acute slices.\nLimitations: Slice age, temperature, agonist delivery and receptor environment are candidate explanations, not a demonstrated resolution.\nEvidence access: Primary abstract\nLack of modulation of nicotinic acetylcholine alpha-7 receptor currents by kynurenic acid in adult hippocampal interneurons. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22848433/ · DOI 10.1371/journal.pone.0041108","source_key":"import-584c58f5-ab9f-53f3-97a9-55783db943b0","source_title":"Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19)","claim_ids":["e67588ea-69fe-5e55-afee-00f23b56b7c5"]},{"conflict_id":"ffd27f79-008d-5738-9d8d-1ceb13b98647","ordinal":2,"label":"No inhibition with prolonged mouse-slice exposure","revision_id":"bfafd789-fdf5-521f-bd28-c662e01ec1ea","start_line":306,"end_line":312,"quote":"## tryptophan-kyna-alpha7-mouse-null\nThe negative receptor result persisted with prolonged high exposure and a positive pharmacological control.\nMouse hippocampal alpha7 currents remained insensitive to kynurenic acid, including slices prepared and stored in 1 mM for over 90 minutes, although glutamatergic currents were blocked.\nModel: Mouse hilar and stratum-radiatum interneuron recordings.\nLimitations: Does not mean kynurenic acid has no neural effects.\nEvidence access: Primary abstract\nLack of modulation of nicotinic acetylcholine alpha-7 receptor currents by kynurenic acid in adult hippocampal interneurons. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22848433/ · DOI 10.1371/journal.pone.0041108","source_key":"import-584c58f5-ab9f-53f3-97a9-55783db943b0","source_title":"Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19)","claim_ids":["3a0a71fb-ba0e-5df3-9858-cd63f9c30306"]}]}],"corrections":[],"research":null}