{"corpus_id":11110487,"paper_sha":"aba93cffa2b4d8aaede1087acd3fe1319ed84b64","doi":"10.1016/S0021-9258(20)71221-4","arxiv_id":null,"pmid":2981834,"pmcid":null,"mag_id":1547972279,"dblp_id":null,"acl_id":null,"title":"Amiloride inhibits phorbol ester-stimulated Na+/H+ exchange and protein kinase C. An amiloride analog selectively inhibits Na+/H+ exchange.","year":1985,"publication_date":"1985-01-25","venue":"Journal of Biological Chemistry","journal":{"name":"The Journal of biological chemistry","pages":"\n          1155-9\n        ","volume":"260 2"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article"],"s2_fields_of_study":["Medicine","Chemistry"],"reference_count":33,"citation_count":174,"influential_citation_count":2,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Amiloride","mj":false,"qs":[{"q":"analogs & derivatives","mj":false,"ui":"Q000031"},{"q":"pharmacology","mj":true,"ui":"Q000494"}],"ui":"D000584"},{"d":"Carrier Proteins","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D002352"},{"d":"Cell Adhesion","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D002448"},{"d":"Cell Differentiation","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D002454"},{"d":"Cell Line","mj":false,"ui":"D002460"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Leukemia, Myeloid, Acute","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D015470"},{"d":"Phorbol 12,13-Dibutyrate","mj":false,"ui":"D015240"},{"d":"Phorbol Esters","mj":false,"qs":[{"q":"pharmacology","mj":true,"ui":"Q000494"}],"ui":"D010703"},{"d":"Phorbols","mj":false,"qs":[{"q":"pharmacology","mj":true,"ui":"Q000494"}],"ui":"D010704"},{"d":"Phosphorylation","mj":false,"ui":"D010766"},{"d":"Protein Kinase C","mj":false,"ui":"D011493"},{"d":"Protein Kinase Inhibitors","mj":true,"ui":"D047428"},{"d":"Pyrazines","mj":false,"qs":[{"q":"pharmacology","mj":true,"ui":"Q000494"}],"ui":"D011719"},{"d":"Receptors, Cell Surface","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D011956"},{"d":"Receptors, Transferrin","mj":false,"ui":"D011990"},{"d":"Sodium-Hydrogen Exchangers","mj":false,"ui":"D017923"}],"chemicals":[{"n":"Carrier Proteins","ui":"D002352","reg":"0"},{"n":"Phorbol Esters","ui":"D010703","reg":"0"},{"n":"Phorbols","ui":"D010704","reg":"0"},{"n":"Protein Kinase Inhibitors","ui":"D047428","reg":"0"},{"n":"Pyrazines","ui":"D011719","reg":"0"},{"n":"Receptors, Cell Surface","ui":"D011956","reg":"0"},{"n":"Receptors, Transferrin","ui":"D011990","reg":"0"},{"n":"Sodium-Hydrogen Exchangers","ui":"D017923","reg":"0"},{"n":"Phorbol 12,13-Dibutyrate","ui":"D015240","reg":"37558-16-0"},{"n":"5-dimethylamiloride","ui":"C039465","reg":"3GC547293P"},{"n":"Amiloride","ui":"D000584","reg":"7DZO8EB0Z3"},{"n":"Protein Kinase C","ui":"D011493","reg":"EC 2.7.11.13"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"The human leukemic cell line, HL-60, differentiates in response to tumor-promoting phorbol esters. Recently, we have reported that one of the first events evoked by phorbol esters in HL-60 cells is the stimulation of Na+-dependent H+ efflux. In efforts to determine whether stimulation of Na+/H+ exchange by phorbol esters is coupled to induction of cellular differentiation, we found that 1) amiloride, a frequently used inhibitor of Na+/H+ exchange, rapidly inhibits phorbol ester-stimulated protein phosphorylation in vivo and protein kinase C-mediated phosphorylation in vitro, both with potency similar to that with which amiloride inhibits Na+/H+ exchange; 2) an amiloride analog, dimethylamiloride, is a far more potent inhibitor of Na+/H+ exchange than is amiloride, while being no more potent than amiloride in inhibiting phorbol ester/protein kinase C-mediated phosphorylation; and 3) at concentrations sufficient to completely inhibit Na+/H+ exchange, amiloride blocked phorbol ester-induced adhesion of HL-60 cells (adhesion being a property indicative of the differentiated state), but dimethylamiloride (as well as ethylisopropylamiloride, another very potent amiloride analog) did not. Thus, dimethylamiloride represents a potential tool for distinguishing protein kinase C-coupled from Na+/H+ exchange-coupled events in phorbol ester-stimulated cells.","claims":[{"public_id":"cl_da7a80a2b805df080658a2f40aaa5960","status":"active","text":"Amiloride inhibits phorbol ester-stimulated protein phosphorylation in vivo and protein kinase C-mediated phosphorylation in vitro with potency similar to that with which it inhibits Na+/H+ exchange.","confidence":0.95,"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["review"],"url":"https://sah.borca.ai/u/3c2apqe3ut"}],"url":"https://sah.borca.ai/claims/cl_da7a80a2b805df080658a2f40aaa5960"},{"public_id":"cl_155bea32250111f9ea70b30f0984ea2b","status":"active","text":"At concentrations sufficient to completely inhibit Na+/H+ exchange, amiloride blocked phorbol ester-induced adhesion of HL-60 cells, whereas dimethylamiloride and ethylisopropylamiloride did not.","confidence":0.93,"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["review"],"url":"https://sah.borca.ai/u/3c2apqe3ut"}],"url":"https://sah.borca.ai/claims/cl_155bea32250111f9ea70b30f0984ea2b"},{"public_id":"cl_0f04706fcc4ffdd8c969fe9f3f1fc7c1","status":"active","text":"Dimethylamiloride can distinguish protein kinase C-coupled events from Na+/H+ exchange-coupled events in phorbol ester-stimulated cells.","confidence":0.9,"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["review"],"url":"https://sah.borca.ai/u/3c2apqe3ut"}],"url":"https://sah.borca.ai/claims/cl_0f04706fcc4ffdd8c969fe9f3f1fc7c1"},{"public_id":"cl_55378b9039af22a13cb179535cc300e7","status":"active","text":"Dimethylamiloride is a far more potent inhibitor of Na+/H+ exchange than amiloride, while being no more potent than amiloride at inhibiting protein kinase C-mediated phosphorylation.","confidence":0.95,"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["review"],"url":"https://sah.borca.ai/u/3c2apqe3ut"}],"url":"https://sah.borca.ai/claims/cl_55378b9039af22a13cb179535cc300e7"}],"concepts":[{"public_id":"co_18e65742c588f9ac2e8ada4a61586b24","status":"active","name":"HL-60 cells","description":"A human leukemic cell line that undergoes differentiation in response to tumor-promoting phorbol esters.","types":["cell line","experimental model"],"aliases":["human leukemic cell line"],"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["review"],"url":"https://sah.borca.ai/u/3c2apqe3ut"}],"url":"https://sah.borca.ai/concepts/co_18e65742c588f9ac2e8ada4a61586b24"},{"public_id":"co_468b30b9e8bcf044358ffdcfe2ce7223","status":"active","name":"cellular differentiation","description":"The process by which HL-60 cells transition to a more mature phenotype in response to phorbol esters, associated with increased adhesion.","types":["cellular process","biological phenomenon"],"aliases":[],"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["review"],"url":"https://sah.borca.ai/u/3c2apqe3ut"}],"url":"https://sah.borca.ai/concepts/co_468b30b9e8bcf044358ffdcfe2ce7223"},{"public_id":"co_66b63e78f441b62934795b502c627bde","status":"active","name":"protein kinase C","description":"A kinase activated by phorbol esters that mediates protein phosphorylation in HL-60 cells and is inhibited by amiloride.","types":["enzyme","signaling molecule"],"aliases":["PKC"],"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["review"],"url":"https://sah.borca.ai/u/3c2apqe3ut"}],"url":"https://sah.borca.ai/concepts/co_66b63e78f441b62934795b502c627bde"},{"public_id":"co_a16d278f39d63cf295296fb6ecde70aa","status":"active","name":"phorbol esters","description":"Tumor-promoting compounds that stimulate Na+/H+ exchange, protein kinase C activity, and differentiation in HL-60 cells.","types":["chemical compound","stimulus"],"aliases":["phorbol ester"],"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["review"],"url":"https://sah.borca.ai/u/3c2apqe3ut"}],"url":"https://sah.borca.ai/concepts/co_a16d278f39d63cf295296fb6ecde70aa"},{"public_id":"co_b5e91ea2255ffec3963f36214098882c","status":"active","name":"amiloride","description":"A compound that inhibits both Na+/H+ exchange and protein kinase C-mediated phosphorylation with similar potency, and blocks phorbol ester-induced HL-60 cell adhesion.","types":["inhibitor","chemical compound"],"aliases":[],"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["review"],"url":"https://sah.borca.ai/u/3c2apqe3ut"}],"url":"https://sah.borca.ai/concepts/co_b5e91ea2255ffec3963f36214098882c"},{"public_id":"co_bbfa10996d1d983dd953e6e281e0eb36","status":"active","name":"protein phosphorylation","description":"A cellular signaling event stimulated by phorbol esters via protein kinase C in HL-60 cells, inhibited by amiloride both in vivo and in vitro.","types":["cellular process","signaling event"],"aliases":[],"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["review"],"url":"https://sah.borca.ai/u/3c2apqe3ut"}],"url":"https://sah.borca.ai/concepts/co_bbfa10996d1d983dd953e6e281e0eb36"},{"public_id":"co_c2e14df166f3fb66ee3acbdef7914543","status":"active","name":"phorbol ester-induced adhesion","description":"Adhesion of HL-60 cells to surfaces following phorbol ester stimulation, used as an indicator of the differentiated cellular state.","types":["cellular phenotype","differentiation marker"],"aliases":[],"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["review"],"url":"https://sah.borca.ai/u/3c2apqe3ut"}],"url":"https://sah.borca.ai/concepts/co_c2e14df166f3fb66ee3acbdef7914543"},{"public_id":"co_d9bb72e37bdb8113b07f214339722136","status":"active","name":"Na+/H+ exchange","description":"A membrane transport mechanism mediating Na+-dependent H+ efflux, stimulated by phorbol esters in HL-60 cells and inhibited by amiloride and its analogs.","types":["transport mechanism","cellular process"],"aliases":["Na+/H+ exchanger","sodium-hydrogen exchange","Na+-dependent H+ efflux"],"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["review"],"url":"https://sah.borca.ai/u/3c2apqe3ut"}],"url":"https://sah.borca.ai/concepts/co_d9bb72e37bdb8113b07f214339722136"},{"public_id":"co_e8010cb660b9a5f88f27cb3fcbbc44c2","status":"active","name":"dimethylamiloride","description":"An amiloride analog that is far more potent than amiloride at inhibiting Na+/H+ exchange but equally potent in inhibiting protein kinase C-mediated phosphorylation, and does not block phorbol ester-induced HL-60 cell adhesion.","types":["inhibitor","chemical compound"],"aliases":["DMA"],"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["review"],"url":"https://sah.borca.ai/u/3c2apqe3ut"}],"url":"https://sah.borca.ai/concepts/co_e8010cb660b9a5f88f27cb3fcbbc44c2"},{"public_id":"co_ea027bd335459143019c11af1415124f","status":"active","name":"ethylisopropylamiloride","description":"A very potent amiloride analog that inhibits Na+/H+ exchange but does not block phorbol ester-induced adhesion of HL-60 cells.","types":["inhibitor","chemical compound"],"aliases":["EIPA"],"contributors":[{"id":170,"public_id":"gsgmdx9r6e","public_label":"pupuri (gsgmdx9r6e)","roles":["extraction"],"url":"https://sah.borca.ai/u/gsgmdx9r6e"},{"id":391,"public_id":"x53qfq3ny9","public_label":"kafkapple (x53qfq3ny9)","roles":["review"],"url":"https://sah.borca.ai/u/x53qfq3ny9"},{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["review"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":136,"public_id":"3c2apqe3ut","public_label":"Anonymous (3c2apqe3ut)","roles":["review"],"url":"https://sah.borca.ai/u/3c2apqe3ut"}],"url":"https://sah.borca.ai/concepts/co_ea027bd335459143019c11af1415124f"}],"external_ids":{"DOI":"10.1016/S0021-9258(20)71221-4","ArXiv":null,"PubMed":2981834,"PubMedCentral":null,"MAG":1547972279,"DBLP":null,"ACL":null},"open_access":{"is_open_access":false,"pdf_url":null,"landing_url":"https://sah.borca.ai/papers/11110487","source":null,"pdf_url_source":null,"license":null,"reason":"pdf_url_not_indexed"},"reference_availability":{"status":"available","references_indexed":true,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":630496,"paper_uid":"ee7aa0bf-052c-49bb-9333-20315e7885fc","canonical_identity":{"paper_id":630496,"paper_uid":"ee7aa0bf-052c-49bb-9333-20315e7885fc","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/11110487"}