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Acetylcholine (<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h) released from preganglionic splanchnic nerves activates nicotinic acetylcholine receptors (<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>s) on chromaffin cells causing membrane depolarization, opening voltage\u2010gated Ca<jats:sup>2+<\/jats:sup>channels (<jats:styled-content style=\"fixed-case\">VGCC<\/jats:styled-content>), and exocytosis of catecholamines and neuropeptides. The serotonin transporter is expressed in<jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>s and interacts with 5\u2010<jats:styled-content style=\"fixed-case\">HT<\/jats:styled-content><jats:sub>1A<\/jats:sub>receptors to control secretion. In addition to blocking the serotonin transporter, some selective serotonin reuptake inhibitors (<jats:styled-content style=\"fixed-case\">SSRI<\/jats:styled-content>s) are also agonists at sigma\u20101 receptors which function as intracellular chaperone proteins and can translocate to the plasma membrane to modulate ion channels. Therefore, we investigated whether<jats:styled-content style=\"fixed-case\">SSRI<\/jats:styled-content>s and other sigma\u20101 receptor ligands can modulate stimulus\u2010secretion coupling in<jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>s. Escitalopram and fluvoxamine (100\u00a0nM to 1\u00a0\u03bcM) reversibly inhibited<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>currents. The sigma\u20101 receptor antagonists<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>\u2010100 and<jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content>\u20101047 also blocked<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>currents (\u2248\u00a050% block at 100\u00a0<jats:styled-content style=\"fixed-case\">nM<\/jats:styled-content>) as did<jats:styled-content style=\"fixed-case\">PRE<\/jats:styled-content>\u2010084, a sigma\u20101 receptor agonist. Block of<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>currents by fluvoxamine and<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>\u2010100 was not additive suggesting a common site of action.<jats:styled-content style=\"fixed-case\">VGCC<\/jats:styled-content>currents were unaffected by the drugs. Neither the increase in cytosolic [Ca<jats:sup>2+<\/jats:sup>] nor the resulting catecholamine secretion evoked by direct membrane depolarization to bypass<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>s was altered by fluvoxamine or<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>\u2010100. However, both Ca<jats:sup>2+<\/jats:sup>entry and catecholamine secretion evoked by the cholinergic agonist carbachol were significantly reduced by fluvoxamine or<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>\u2010100. Together, our data suggest that sigma\u20101 receptors do not acutely regulate catecholamine secretion. Rather,<jats:styled-content style=\"fixed-case\">SSRI<\/jats:styled-content>s and other sigma\u20101 receptor ligands inhibit secretion evoked by cholinergic stimulation because of direct block of Ca<jats:sup>2+<\/jats:sup>entry via<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>s.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14149-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14149","type":"journal-article","created":{"date-parts":[[2017,8,17]],"date-time":"2017-08-17T07:22:54Z","timestamp":1502954574000},"page":"171-182","source":"Crossref","is-referenced-by-count":10,"title":["Sigma\u20101 receptor ligands inhibit catecholamine secretion from 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