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• W2746827679 abstract "Abstract Adrenal chromaffin cells ( ACC s) are the neuroendocrine arm of the sympathetic nervous system and key mediators of the physiological stress response. Acetylcholine ( AC h) released from preganglionic splanchnic nerves activates nicotinic acetylcholine receptors ( nAChR s) on chromaffin cells causing membrane depolarization, opening voltage‐gated Ca 2+ channels ( VGCC ), and exocytosis of catecholamines and neuropeptides. The serotonin transporter is expressed in ACC s and interacts with 5‐ HT 1A receptors to control secretion. In addition to blocking the serotonin transporter, some selective serotonin reuptake inhibitors ( SSRI s) are also agonists at sigma‐1 receptors which function as intracellular chaperone proteins and can translocate to the plasma membrane to modulate ion channels. Therefore, we investigated whether SSRI s and other sigma‐1 receptor ligands can modulate stimulus‐secretion coupling in ACC s. Escitalopram and fluvoxamine (100 nM to 1 μM) reversibly inhibited nAChR currents. The sigma‐1 receptor antagonists NE ‐100 and BD ‐1047 also blocked nAChR currents (≈ 50% block at 100 nM ) as did PRE ‐084, a sigma‐1 receptor agonist. Block of nAChR currents by fluvoxamine and NE ‐100 was not additive suggesting a common site of action. VGCC currents were unaffected by the drugs. Neither the increase in cytosolic [Ca 2+ ] nor the resulting catecholamine secretion evoked by direct membrane depolarization to bypass nAChR s was altered by fluvoxamine or NE ‐100. However, both Ca 2+ entry and catecholamine secretion evoked by the cholinergic agonist carbachol were significantly reduced by fluvoxamine or NE ‐100. Together, our data suggest that sigma‐1 receptors do not acutely regulate catecholamine secretion. Rather, SSRI s and other sigma‐1 receptor ligands inhibit secretion evoked by cholinergic stimulation because of direct block of Ca 2+ entry via nAChR s. image" @default.
• W2746827679 created "2017-08-31" @default.
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• W2746827679 date "2017-09-19" @default.
• W2746827679 modified "2023-10-14" @default.
• W2746827679 title "Sigma-1 receptor ligands inhibit catecholamine secretion from adrenal chromaffin cells due to block of nicotinic acetylcholine receptors" @default.
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• W2746827679 doi "https://doi.org/10.1111/jnc.14149" @default.
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