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

Brindley RL, Bauer MB, Blakely RD, Currie KPM
Neuropharmacology. 2016 110 (Pt A): 438-448

PMID: 27544824 · PMCID: PMC5028315 · DOI:10.1016/j.neuropharm.2016.08.015

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 ≈ 750 fold lower abundance than adrenaline, and in SERT(-/-) mice this was reduced by ≈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 Ca(2+) channels, K(+) channels, or intracellular [Ca(2+)] 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.

Copyright © 2016 Elsevier Ltd. All rights reserved.

MeSH Terms (17)

Adrenal Glands Animals Calcium Calcium Channels, N-Type Cations, Divalent Cells, Cultured Chromaffin Cells Exocytosis Male Membrane Potentials Mice, Inbred C57BL Mice, Knockout Potassium Channels, Voltage-Gated Receptors, Serotonin Serotonin Serotonin Agents Serotonin Plasma Membrane Transport Proteins

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