{"id":"78aaf931-fe4d-584a-9efa-02200cd5cf8b","stable_key":"05a3cf47-e660-5ab3-8c32-5eba9847cf0a:thc-dagla-makes-2ag","predicate":"produces","statement":"The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"5842f768-ba0d-541d-a28e-6843f31ded4a","mechanism_event_label":"One enzyme makes the messenger that carries the backwards signal.","subject":{"id":"db61034c-b170-5491-acb0-c955ce2e2251","slug":"dagla","display_name":"Diacylglycerol lipase alpha / DAGLA","entity_type_key":"protein"},"object":{"id":"e0aeb1b3-fbfb-5ac4-a29c-d5171072c256","slug":"2-arachidonoylglycerol","display_name":"2-Arachidonoylglycerol / 2-AG","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"5842f768-ba0d-541d-a28e-6843f31ded4a","stable_key":"05a3cf47-e660-5ab3-8c32-5eba9847cf0a:thc-dagla-makes-2ag-event","event_type":"biochemical_relationship","label":"One enzyme makes the messenger that carries the backwards signal.","description":"The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a85d7dbe-0f18-506e-9cec-8890abf60b3c","slug":"retrograde-signalling","display_name":"Retrograde endocannabinoid signalling from postsynaptic neuron to presynaptic terminal","entity_type_key":"cellular_process"},"role":"downstream_process","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"db61034c-b170-5491-acb0-c955ce2e2251","slug":"dagla","display_name":"Diacylglycerol lipase alpha / DAGLA","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e0aeb1b3-fbfb-5ac4-a29c-d5171072c256","slug":"2-arachidonoylglycerol","display_name":"2-Arachidonoylglycerol / 2-AG","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/thc-research/20159446.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a83e761bbc9dd85f5c5ec84424a876a33b0914b1e6723ed809db0b1854cf00ed\", \"start_char\": 0, \"end_char\": 1097, \"text_sha256\": \"a83e761bbc9dd85f5c5ec84424a876a33b0914b1e6723ed809db0b1854cf00ed\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Conditional and constitutive DAGLα manipulation with synaptic recordings","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"DAGLα deletion with retrograde suppression measurement","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Assigns the retrograde messenger to a specific enzyme product by removing the enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates.","comparator":null,"unit":null,"notes":"","entity":{"slug":"tetrahydrocannabinol","display_name":"Delta-9-tetrahydrocannabinol / THC","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"One enzyme makes the messenger that carries the backwards signal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[thc-p20159446] The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission. (2010). https://pubmed.ncbi.nlm.nih.gov/20159446/ DOI: 10.1016/j.neuron.2010.01.021","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Brain slices","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"3f686e5f-610a-5da8-8c60-8237f39e901d","evidence_kind":"source_excerpt","locator":"Lines 322-333","start_line":322,"end_line":333,"excerpt":"### thc-dagla-makes-2ag\nThe endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission.\nCondition category: machinery_impairment\nnutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates.\nplain_language: One enzyme makes the messenger that carries the backwards signal.\norganism: Mouse\ntissue_or_cell_type: Brain slices\nexperimental_model: Conditional and constitutive DAGLα manipulation with synaptic recordings\nlimitations: Assigns the retrograde messenger to a specific enzyme product by removing the enzyme.\nexposure: DAGLα deletion with retrograde suppression measurement\nevidence_span: {\"source_cache\": \"artifacts/thc-research/20159446.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a83e761bbc9dd85f5c5ec84424a876a33b0914b1e6723ed809db0b1854cf00ed\", \"start_char\": 0, \"end_char\": 1097, \"text_sha256\": \"a83e761bbc9dd85f5c5ec84424a876a33b0914b1e6723ed809db0b1854cf00ed\"}\n[thc-p20159446] The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission. (2010). https://pubmed.ncbi.nlm.nih.gov/20159446/ DOI: 10.1016/j.neuron.2010.01.021","model_system":"Conditional and constitutive DAGLα manipulation with synaptic recordings","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [thc-p20159446] The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission. (2010). https://pubmed.ncbi.nlm.nih.gov/20159446/ DOI: 10.1016/j.neuron.2010.01.021","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"b4367320-9724-507a-bead-6932fa0a78cb","stable_key":"import-05a3cf47-e660-5ab3-8c32-5eba9847cf0a","title":"THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21)","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":"60abc81737d18b7a50b01ca487e38291774ee15d9777651aa2d3eac8670ac3b2","revision_id":"2cba3552-af89-580d-b20a-8cfb1b14f9e7","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}