{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:35:14Z","timestamp":1791297314218,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":334,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>Intracellular pH (pH<jats:sub>i<\/jats:sub>) in heart is regulated by sarcolemmal H<jats:sup>+<\/jats:sup>\u2010equivalent transporters such as Na<jats:sup>+<\/jats:sup>\u2010H<jats:sup>+<\/jats:sup>exchange (NHE) and Na<jats:sup>+<\/jats:sup>\u2010HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>cotransport (NBC). Inhibition of NBC influences pH<jats:sub>i<\/jats:sub>and can be cardioprotective in animal models of post\u2010ischaemic reperfusion. Apart from a rabbit polyclonal NBC\u2010antibody, a selective NBC inhibitor compound has not been studied. Compound S0859 (C<jats:sub>29<\/jats:sub>H<jats:sub>24<\/jats:sub>ClN<jats:sub>3<\/jats:sub>O<jats:sub>3<\/jats:sub>S) is a putative NBC inhibitor. Here, we provide the drug's chemical structure, test its potency and selectivity in ventricular cells and assess its suitability for experiments on cardiac contraction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>pH<jats:sub>i<\/jats:sub>recovery from intracellular acidosis was monitored using pH\u2010epifluorescence (SNARF\u2010fluorophore) in guinea pig, rat and rabbit isolated ventricular myocytes. Electrically evoked cell shortening (contraction) was measured optically. With CO<jats:sub>2<\/jats:sub>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>\u2010buffered superfusates containing 30\u2003\u03bcM cariporide (to inhibit NHE), pH<jats:sub>i<\/jats:sub>recovery is mediated by NBC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>S0859, an<jats:italic>N<\/jats:italic>\u2010cyanosulphonamide compound, reversibly inhibited NBC\u2010mediated pH<jats:sub>i<\/jats:sub>recovery (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>=1.7\u2003\u03bcM, full inhibition at \u223c30\u2003\u03bcM). In HEPES\u2010buffered superfusates, NHE\u2010mediated pH<jats:sub>i<\/jats:sub>recovery was unaffected by 30\u2003\u03bcM S0859. With CO<jats:sub>2<\/jats:sub>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>buffer, pH<jats:sub>i<\/jats:sub>recovery from intracellular alkalosis (mediated by Cl<jats:sup>\u2212<\/jats:sup>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>and Cl<jats:sup>\u2212<\/jats:sup>\/OH<jats:sup>\u2212<\/jats:sup>exchange) was also unaffected. Selective NBC\u2010inhibition was not due to action on carbonic anhydrase (CA) enzymes, as 100\u2003\u03bcM acetazolamide (a membrane\u2010permeant CA\u2010inhibitor) had no significant effect on NBC activity. pH<jats:sub>i<\/jats:sub>recovery from acidosis was associated with increased contractile\u2010amplitude. The time course of recovery of pH<jats:sub>i<\/jats:sub>and contraction was slowed by S0859, confirming that NBC is a significant controller of contractility during acidosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>Compound S0859 is a selective, high\u2010affinity generic NBC inhibitor, potentially important for probing the transporter's functional role in heart and other tissues.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2008)<jats:bold>153<\/jats:bold>, 972\u2013982; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0707667\">10.1038\/sj.bjp.0707667<\/jats:ext-link>; published online 21 January 2008<\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0707667","type":"journal-article","created":{"date-parts":[[2008,1,21]],"date-time":"2008-01-21T13:23:52Z","timestamp":1200921832000},"page":"972-982","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["S0859, an<i>N<\/i>\u2010cyanosulphonamide inhibitor of sodium\u2010bicarbonate cotransport in the heart"],"prefix":"10.1111","volume":"153","author":[{"given":"F F\u2010T","family":"Ch'En","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F C","family":"Villafuerte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Swietach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P M","family":"Cobden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R D","family":"Vaughan\u2010Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.137bf.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0353124"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01693-5"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M700066200"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.55.3.382"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1989.sp017833"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00370705"},{"key":"e_1_2_8_9_1","unstructured":"Ch'enFF Vaughan\u2010JonesRD(2001).Effect of S0859 a putative Na+\u2010HCO3\u2212co\u2010transport inhibitor on intracellular pH regulation in the guinea\u2010pig ventricular myocyte.Proceedings of the 34th International Congress of Physiological Sciences; New Zealand ID no. 1495 (Abstract)."},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/35014615"},{"issue":"3","key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"C576","DOI":"10.1152\/ajpcell.1999.276.3.C576","article-title":"Cloning and characterization of a human electrogenic Na+\u2010HCO3 \u2212 cotransporter isoform (hhNBC)","volume":"276","author":"Choi I","year":"1999","journal-title":"Am J Physiol"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.626929"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705749"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00713.2005"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.12.7.1123"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-003-1067-2"},{"issue":"2","key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"C348","DOI":"10.1152\/ajpcell.1992.262.2.C348","article-title":"Contraction and intracellular Ca2+, Na+, and H+ during acidosis in rat ventricular myocytes","volume":"262","author":"Harrison SM","year":"1992","journal-title":"Am J Physiol"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704405"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(01)00430-8"},{"key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/S0022-3565(24)29535-5","article-title":"A novel sodium\u2010hydrogen exchanger isoform\u20101 inhibitor, zoniporide, reduces ischemic myocardial injury in vitro and in vivo","volume":"297","author":"Knight DR","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019422"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(85)80119-X"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.0159z.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.471bn.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.487bn.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602181200"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.16.040176.001521"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0223-5234(03)00100-4"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/28.9.1312"},{"issue":"6","key":"e_1_2_8_30_1","doi-asserted-by":"crossref","first-page":"C967","DOI":"10.1152\/ajpcell.1990.258.6.C967","article-title":"Effects of changes of pH on the contractile function of cardiac muscle","volume":"258","author":"Orchard CH","year":"1990","journal-title":"Am J Physiol"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2640409"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.23.16569"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050417"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-003-1180-2"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.278.5.H1457"},{"key":"e_1_2_8_36_1","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S0008-6363(96)88579-8","article-title":"Protective effects of HOE642, a selective sodium\u2010hydrogen exchange subtype 1 inhibitor, on cardiac ischaemia and reperfusion","volume":"29","author":"Scholz W","year":"1995","journal-title":"Cardiovasc Res"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb13607.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.092957"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1109\/10.1375"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021574"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.10025"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00578a012"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00589.2001"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.8.723"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.071068"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.278.1.H300"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0707667","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0707667","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0707667","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T23:11:10Z","timestamp":1737846670000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0707667"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,3]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2008,3]]}},"alternative-id":["10.1038\/sj.bjp.0707667"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0707667","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,3]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}