{"id":"17436b25-ff9c-5a1d-bd3d-7ea9a617db5b","stable_key":"fe6af7fc-7372-5c4f-9c2f-2bbf56695397:phosphorus-tenapanor-nhe3","predicate":"inhibits","statement":"Tenapanor inhibits intestinal NHE3, the sodium/hydrogen exchanger targeted in the phosphate-absorption study.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"180dd820-1529-5111-b028-31c4095a7909","mechanism_event_label":"A sodium-handling protein can change how phosphate crosses the gut wall.","subject":{"id":"b4ff4376-9fb0-5ab7-bdfa-fb7efce7c2b0","slug":"tenapanor","display_name":"Tenapanor","entity_type_key":"small_molecule"},"object":{"id":"ad5210f7-a9b7-51d0-843b-46a808c47271","slug":"slc9a3","display_name":"Human sodium/hydrogen exchanger 3 / SLC9A3","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"180dd820-1529-5111-b028-31c4095a7909","stable_key":"fe6af7fc-7372-5c4f-9c2f-2bbf56695397:phosphorus-tenapanor-nhe3-event","event_type":"biochemical_relationship","label":"A sodium-handling protein can change how phosphate crosses the gut wall.","description":"Tenapanor inhibits intestinal NHE3, the sodium/hydrogen exchanger targeted in the phosphate-absorption study.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"38de8704-84db-5770-ac1d-242cd787e798","slug":"sodium-ion","display_name":"Sodium ion","entity_type_key":"ion"},"role":"transported_ion","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b4ff4376-9fb0-5ab7-bdfa-fb7efce7c2b0","slug":"tenapanor","display_name":"Tenapanor","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ad5210f7-a9b7-51d0-843b-46a808c47271","slug":"slc9a3","display_name":"Human sodium/hydrogen exchanger 3 / SLC9A3","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/phosphorus-research/30158152.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e\", \"start_char\": 0, \"end_char\": 1701, \"text_sha256\": \"6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Rodent physiology, human enteroid transport and healthy-volunteer intervention","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Phosphorus research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"phosphorus","display_name":"Phosphorus","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human-derived intestinal epithelial system","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A sodium-handling protein can change how phosphate crosses the gut wall.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Intestinal epithelium; stool and urinary balance","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8792a0ff-ffc6-53db-aa8d-6591c7652a4f","evidence_kind":"source_excerpt","locator":"Lines 321-332","start_line":321,"end_line":332,"excerpt":"### phosphorus-tenapanor-nhe3\nTenapanor inhibits intestinal NHE3, the sodium/hydrogen exchanger targeted in the phosphate-absorption study.\nCondition category: normal\nnutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A sodium-handling protein can change how phosphate crosses the gut wall.\norganism: Human-derived intestinal epithelial system\ntissue_or_cell_type: Intestinal epithelium; stool and urinary balance\nexperimental_model: Rodent physiology, human enteroid transport and healthy-volunteer intervention\nlimitations: Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score.\nexposure: Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days\nevidence_span: {\"source_cache\": \"artifacts/phosphorus-research/30158152.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e\", \"start_char\": 0, \"end_char\": 1701, \"text_sha256\": \"6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e\"}\n[phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474","model_system":"Rodent physiology, human enteroid transport and healthy-volunteer intervention","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"cfdefe70-3a09-5e2e-97c8-46626382e4b4","stable_key":"import-fe6af7fc-7372-5c4f-9c2f-2bbf56695397","title":"Phosphorus: metabolism, signaling and nutrient connections (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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