An interplay between the serotonin transporter (SERT) and 5-HT receptors controls stimulus-secretion coupling in sympathoadrenal chromaffin cells

作者：Brindley Rebecca L; Bauer Mary Beth; Blakely Randy D; Currie Kevin P M^*

来源：Neuropharmacology, 2016, 110: 438-448.

DOI：10.1016/j.neuropharm.2016.08.015

• Serotonin transporter
• Adrenal chromaffin cell
• Calcium channel
• Exocytosis
• Catecholamine
• 5-HT receptor
• Amperometry
• Calcium imaging
• GPCR

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.

• 出版日期2016-11