{"id":"fa8e7e1d-90d8-52c2-bf96-fdb1fed0a2e6","stable_key":"4df6a932-097e-563a-91fe-5dceec471ffd:chloride-macula-transport-renin","predicate":"transport_blockade_increases","statement":"Luminal bumetanide increased renin release during high-NaCl perfusion, supporting cotransporter-dependent sensing.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"15333fd5-73ea-54a9-a971-390e726d4b45","mechanism_event_label":"The chloride must engage the transport system to produce the usual signal.","subject":{"id":"a278ff7a-e80e-5969-b408-a2c2b455f496","slug":"slc12a1","display_name":"Sodium-potassium-chloride cotransporter 2","entity_type_key":"protein"},"object":{"id":"78d44150-e83e-5ff4-ac6c-cf395b173571","slug":"renin-secretion","display_name":"Juxtaglomerular renin secretion","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"15333fd5-73ea-54a9-a971-390e726d4b45","stable_key":"4df6a932-097e-563a-91fe-5dceec471ffd:chloride-macula-transport-renin-event","event_type":"biochemical_relationship","label":"The chloride must engage the transport system to produce the usual signal.","description":"Luminal bumetanide increased renin release during high-NaCl perfusion, supporting cotransporter-dependent sensing.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6f35aa38-f875-5759-b749-97a2f6480ff3","slug":"chloride-ion","display_name":"Chloride ion","entity_type_key":"ion"},"role":"luminal_substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"38de8704-84db-5770-ac1d-242cd787e798","slug":"sodium-ion","display_name":"Sodium ion","entity_type_key":"ion"},"role":"cotransported_ion","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5dd31e52-f51e-51f3-880e-240abcc0ab1d","slug":"potassium-ion","display_name":"Potassium ion","entity_type_key":"ion"},"role":"cotransported_ion","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"a278ff7a-e80e-5969-b408-a2c2b455f496","slug":"slc12a1","display_name":"Sodium-potassium-chloride cotransporter 2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"78d44150-e83e-5ff4-ac6c-cf395b173571","slug":"renin-secretion","display_name":"Juxtaglomerular renin secretion","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/chloride-research/2012204.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac\", \"start_char\": 0, \"end_char\": 1695, \"text_sha256\": \"8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Perfused isolated juxtaglomerular apparatus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Luminal ion substitutions and 1 µM bumetanide","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Pharmacological evidence for macula-densa Na-K-2Cl transport; molecular NKCC2 was not genetically tested in this experiment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Chloride research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"chloride","display_name":"Chloride","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Rabbit","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The chloride must engage the transport system to produce the usual signal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[chloride-p2012204] Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport. (1991). https://pubmed.ncbi.nlm.nih.gov/2012204/ DOI: 10.1152/ajprenal.1991.260.4.f486","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Macula densa and renin-secreting apparatus","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"f6249897-b588-5810-9278-4144f3dcc075","evidence_kind":"source_excerpt","locator":"Lines 575-586","start_line":575,"end_line":586,"excerpt":"### chloride-macula-transport-renin\nLuminal bumetanide increased renin release during high-NaCl perfusion, supporting cotransporter-dependent sensing.\nCondition category: normal\nnutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The chloride must engage the transport system to produce the usual signal.\norganism: Rabbit\ntissue_or_cell_type: Macula densa and renin-secreting apparatus\nexperimental_model: Perfused isolated juxtaglomerular apparatus\nlimitations: Pharmacological evidence for macula-densa Na-K-2Cl transport; molecular NKCC2 was not genetically tested in this experiment.\nexposure: Luminal ion substitutions and 1 µM bumetanide\nevidence_span: {\"source_cache\": \"artifacts/chloride-research/2012204.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac\", \"start_char\": 0, \"end_char\": 1695, \"text_sha256\": \"8ce0dd9b0315d2f3148f4edcc7d2e511984122ac2d50fa813a03e9b473b73dac\"}\n[chloride-p2012204] Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport. 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