期刊
NEUROPHARMACOLOGY
卷 110, 期 -, 页码 438-448出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2016.08.015
关键词
Serotonin transporter; Adrenal chromaffin cell; Calcium channel; Exocytosis; Catecholamine; 5-HT receptor; Amperometry; Calcium imaging; GPCR
资金
- National Institutes of Health [R21 NS081429]
- Vanderbilt Conte Center - National Institutes of Health [P50 M096972]
- Department of Anesthesiology at Vanderbilt University Medical Center
Adrenal chromaffin cells (ACCs), the neuroendocrine arm of the sympathetic nervous system, secrete catecholamines to mediate the physiological response to stress. Although ACCs do not synthesize 5-HT, they express the serotonin transporter (SERT). Genetic variations in SERT are linked to several CNS disorders but the role(s) of SERT/5-HT in ACCs has remained unclear. Adrenal glands from wild-type mice contained 5-HT at approximate to 750 fold lower abundance than adrenaline, and in SERT-/- mice this was reduced by,approximate to 80% with no change in catecholamines. Carbon fibre amperometry showed that SERT modulated the ability of 5-HT1A receptors to inhibit exocytosis. 5-HT reduced the number of amperometric spikes (vesicular fusion events) evoked by KCl in SERT-/- cells and wild-type cells treated with escitalopram, a SERT antagonist. The 5-HT1A receptor antagonist WAY100635 blocked the inhibition by 5-HT which was mimicked by the 5-HT1A agonist 8-OH-DPAT but not the 5-HT1B agonist CP93129. There was no effect on voltage-gated Ca2+ channels, K+ channels, or intracellular [Ca2+] handling, showing the 5-HT receptors recruit an atypical inhibitory mechanism. Spike charge and kinetics were not altered by 5-HT receptors but were reduced in SERT-/- cells compared to wild-type cells. Our data reveal a novel role for SERT and suggest that adrenal chromaffin cells might be a previously unrecognized hub for serotonergic control of the sympathetic stress response. (C) 2016 Elsevier Ltd. All rights reserved.
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