{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:04:06Z","timestamp":1789772646651,"version":"4.0.1"},"reference-count":43,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2015,7,8]],"date-time":"2015-07-08T00:00:00Z","timestamp":1436313600000},"content-version":"vor","delay-in-days":0,"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":[[2015,8]]},"abstract":"Background and Purpose<\/jats:title>T16A<\/jats:styled-content>inh<\/jats:sub>\u2010A<\/jats:styled-content>01, C<\/jats:styled-content>aCC<\/jats:styled-content>inh<\/jats:sub>\u2010A<\/jats:styled-content>01 and MONNA<\/jats:styled-content> are identified as selective inhibitors of the TMEM16A<\/jats:styled-content> calcium\u2010activated chloride channel (CaCC<\/jats:styled-content>). The aim of this study was to examine the chloride\u2010specificity of these compounds on isolated resistance arteries in the presence and absence (\u00b1) of extracellular chloride.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>Isolated resistance arteries were maintained in a myograph and tension recorded, in some instances combined with microelectrode impalement for membrane potential measurements or intracellular calcium monitoring using fura\u20102. Voltage\u2010dependent calcium currents (VDCC<\/jats:styled-content>) were measured in A<\/jats:styled-content>7r5 cells with voltage\u2010clamp electrophysiology using barium as a charge carrier.<\/jats:p><\/jats:sec>Key Results<\/jats:title>Rodent arteries preconstricted with noradrenaline or U<\/jats:styled-content>46619 were concentration\u2010dependently relaxed by T<\/jats:styled-content>16A<\/jats:styled-content>inh<\/jats:sub>\u2010A<\/jats:styled-content>01 (0.1\u201310\u2009\u03bcM<\/jats:styled-content>): IC<\/jats:styled-content>50<\/jats:sub> and maximum relaxation were equivalent in \u00b1chloride (30\u2009min aspartate substitution) and the T<\/jats:styled-content>16A<\/jats:styled-content>inh<\/jats:sub>\u2010A<\/jats:styled-content>01\u2010induced vasorelaxation \u00b1chloride were accompanied by membrane hyperpolarization and lowering of intracellular calcium. However, agonist concentration\u2013response curves \u00b1chloride, with 10\u2009\u03bcM T<\/jats:styled-content>16A<\/jats:styled-content>inh<\/jats:sub>\u2010A<\/jats:styled-content>01 present, achieved similar maximum constrictions although agonist\u2010sensitivity decreased. Contractions induced by elevated extracellular potassium were concentration\u2010dependently relaxed by T<\/jats:styled-content>16A<\/jats:styled-content>inh<\/jats:sub>\u2010A<\/jats:styled-content>01 \u00b1chloride. Moreover, T<\/jats:styled-content>16A<\/jats:styled-content>inh<\/jats:sub>\u2010A<\/jats:styled-content>01 inhibited VDCCs<\/jats:styled-content> in A<\/jats:styled-content>7r5 cells in a concentration\u2010dependent manner. CaCC<\/jats:styled-content>inh<\/jats:sub>\u2010A<\/jats:styled-content>01 and MONNA<\/jats:styled-content> (0.1\u201310\u2009\u03bcM) induced vasorelaxation \u00b1chloride and both compounds lowered maximum contractility. MONNA,<\/jats:styled-content> 10\u2009\u03bcM, induced substantial membrane hyperpolarization under resting conditions.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>T<\/jats:styled-content>16A<\/jats:styled-content>inh<\/jats:sub>\u2010A<\/jats:styled-content>01, CaCC<\/jats:styled-content>inh<\/jats:sub>\u2010A<\/jats:styled-content>01 and MONNA<\/jats:styled-content> concentration\u2010dependently relax rodent resistance arteries, but an equivalent vasorelaxation occurs when the transmembrane chloride gradient is abolished with an impermeant anion. These compounds therefore display poor selectivity for TMEM16A<\/jats:styled-content> and inhibition of CaCC<\/jats:styled-content> in vascular tissue in the concentration range that inhibits the isolated conductance.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13201","type":"journal-article","created":{"date-parts":[[2015,5,25]],"date-time":"2015-05-25T20:39:05Z","timestamp":1432586345000},"page":"4158-4172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["New selective inhibitors of calcium\u2010activated chloride channels \u2013 T<\/scp>16A<\/scp>inh<\/sub>\u2010A<\/scp>01, C<\/scp>aCC<\/scp>inh<\/sub>\u2010A<\/scp>01 and MONNA<\/scp> \u2013 what do they inhibit?"],"prefix":"10.1111","volume":"172","author":[{"given":"D M B","family":"Boedtkjer","sequence":"first","affiliation":[{"name":"Department of Biomedicine Aarhus University Aarhus Denmark"},{"name":"Department of Cardiothoracic and Vascular Surgery Aarhus University Hospital Skejby Denmark"},{"name":"Department of Gynaecology and Obstetrics Aarhus University Hospital Skejby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A B","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V M","family":"Matchkov","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K E","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University Aarhus Denmark"},{"name":"Department of Gynaecology and Obstetrics Aarhus University Hospital Skejby Denmark"},{"name":"Aarhus Institute of Advanced Studies Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00476.2012"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1983.sp014575"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12447"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.549188"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-008-0532-3"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.4161\/chan.28065"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.418"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1163518"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6107(00)00024-9"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-013-1382-1"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02199.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701431"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.043208"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00044.2012"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1211594110"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-013-9532-0"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2011.058206"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1984.sp015275"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1572-5"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.189506"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-013-1380-3"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.09.022"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00873.x"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.41.1.19"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.175109"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.1998.00435.x"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.113.087502"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000164090.04069.22"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1143"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-004-0659-x"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.116.6.825"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/19336950.2015.1027849"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.068544"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.1.211"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000156448.74296.FE"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1598-8"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.09.003"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.232520"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00404.2011"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2009.11.026"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.07.036"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07313"}],"container-title":["British 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