{"id":"c3dc8a2a-8b18-5c89-bc10-fe9fa49a59b2","stable_key":"c953cca8-774f-596d-b27a-f13c2c0b5fce:dhc-t-type-inhibition","predicate":"inhibits","statement":"Capsaicin, dihydrocapsaicin, N-VAMC8, N-VAMC9 and N-VAMC10 directly and partially reversibly inhibited low-voltage-activated T-type calcium channels, whereas olvanil, capsiate and vanillylamine could not, and the capsaicin inhibition of T-type channels was independent of TRPV1 activation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"a7c40b5d-8676-593d-9180-22f9d19e858a","mechanism_event_label":"Both compounds shut down a second kind of calcium channel in pain neurons, again without the receptor.","subject":{"id":"6259a8e0-9611-5f60-9e1b-53bbd8eb1afd","slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"},"object":{"id":"f1b679d9-7cfb-5518-87a6-7ef2e603ac62","slug":"t-type-calcium-channel","display_name":"Low-voltage-activated T-type voltage-dependent calcium channels","entity_type_key":"protein_family"},"evidence_count":1,"mechanism_event":{"id":"a7c40b5d-8676-593d-9180-22f9d19e858a","stable_key":"c953cca8-774f-596d-b27a-f13c2c0b5fce:dhc-t-type-inhibition-event","event_type":"biochemical_relationship","label":"Both compounds shut down a second kind of calcium channel in pain neurons, again without the receptor.","description":"Capsaicin, dihydrocapsaicin, N-VAMC8, N-VAMC9 and N-VAMC10 directly and partially reversibly inhibited low-voltage-activated T-type calcium channels, whereas olvanil, capsiate and vanillylamine could not, and the capsaicin inhibition of T-type channels was independent of TRPV1 activation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9cdd3a64-5185-5998-82a6-d25c8409b998","slug":"capsaicin","display_name":"Capsaicin","entity_type_key":"small_molecule"},"role":"co_active_compound","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8e0c61d8-3930-51d5-bce2-25a5edfb797c","slug":"human-trpv1","display_name":"Human transient receptor potential vanilloid 1 / TRPV1","entity_type_key":"protein"},"role":"excluded_mediator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7f3c783b-41b0-5f2b-ada9-344a5f8b5624","slug":"capsiate","display_name":"Capsiate, a non-pungent capsinoid ester","entity_type_key":"chemical_species"},"role":"inactive_analogue","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6259a8e0-9611-5f60-9e1b-53bbd8eb1afd","slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"f1b679d9-7cfb-5518-87a6-7ef2e603ac62","slug":"t-type-calcium-channel","display_name":"Low-voltage-activated T-type voltage-dependent calcium channels","entity_type_key":"protein_family"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dihydrocapsaicin-research/17362879.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"7e28fe88d1e616cf4d60ccadcf38ae9b0890891513dcda0d9623e5d3579d7201\", \"start_char\": 0, \"end_char\": 1243, \"text_sha256\": \"7e28fe88d1e616cf4d60ccadcf38ae9b0890891513dcda0d9623e5d3579d7201\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Enzymatically synthesised capsaicin analogues applied to voltage-dependent calcium channels","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Capsaicin, dihydrocapsaicin, N-VAMC8, N-VAMC9, N-VAMC10, olvanil, capsiate and vanillylamine on T-type channels","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A second TRPV1-independent target, with a clear structural boundary: the ester analogue and the free amine do not do it. The channel work is in isolated preparations.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dihydrocapsaicin","display_name":"Dihydrocapsaicin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Sensory neuron preparations","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Both compounds shut down a second kind of calcium channel in pain neurons, again without the receptor.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dhc-p17362879] Enzymatic synthesis of capsaicin analogs and their effect on the T-type Ca2+ channels. 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The channel work is in isolated preparations.\nexposure: Capsaicin, dihydrocapsaicin, N-VAMC8, N-VAMC9, N-VAMC10, olvanil, capsiate and vanillylamine on T-type channels\nevidence_span: {\"source_cache\": \"artifacts/dihydrocapsaicin-research/17362879.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"7e28fe88d1e616cf4d60ccadcf38ae9b0890891513dcda0d9623e5d3579d7201\", \"start_char\": 0, \"end_char\": 1243, \"text_sha256\": \"7e28fe88d1e616cf4d60ccadcf38ae9b0890891513dcda0d9623e5d3579d7201\"}\n[dhc-p17362879] Enzymatic synthesis of capsaicin analogs and their effect on the T-type Ca2+ channels. 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