Format

Send to

Choose Destination
ACS Chem Neurosci. 2017 May 17;8(5):943-954. doi: 10.1021/acschemneuro.7b00026. Epub 2017 Apr 13.

Serotonin and Serotonin Transporters in the Adrenal Medulla: A Potential Hub for Modulation of the Sympathetic Stress Response.

Author information

1
Department of Anesthesiology, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
2
Department of Biomedical Science, Charles E. Schmidt College of Medicine, and Florida Atlantic University Brain Institute, Florida Atlantic University , Jupiter, Florida 33458, United States.
3
Department of Pharmacology, Vanderbilt University , Nashville, Tennessee 37232, United States.

Abstract

Serotonin (5-HT) is an important neurotransmitter in the central nervous system where it modulates circuits involved in mood, cognition, movement, arousal, and autonomic function. The 5-HT transporter (SERT; SLC6A4) is a key regulator of 5-HT signaling, and genetic variations in SERT are associated with various disorders including depression, anxiety, and autism. This review focuses on the role of SERT in the sympathetic nervous system. Autonomic/sympathetic dysfunction is evident in patients with depression, anxiety, and other diseases linked to serotonergic signaling. Experimentally, loss of SERT function (SERT knockout mice or chronic pharmacological block) has been reported to augment the sympathetic stress response. Alterations to serotonergic signaling in the CNS and thus central drive to the peripheral sympathetic nervous system are presumed to underlie this augmentation. Although less widely recognized, SERT is robustly expressed in chromaffin cells of the adrenal medulla, the neuroendocrine arm of the sympathetic nervous system. Adrenal chromaffin cells do not synthesize 5-HT but accumulate small amounts by SERT-mediated uptake. Recent evidence demonstrated that 5-HT1A receptors inhibit catecholamine secretion from adrenal chromaffin cells via an atypical mechanism that does not involve modulation of cellular excitability or voltage-gated Ca2+ channels. This raises the possibility that the adrenal medulla is a previously unrecognized peripheral hub for serotonergic control of the sympathetic stress response. As a framework for future investigation, a model is proposed in which stress-evoked adrenal catecholamine secretion is fine-tuned by SERT-modulated autocrine 5-HT signaling.

KEYWORDS:

5-HT receptor; Serotonin transporter; adrenal chromaffin cell; calcium channel; catecholamine; exocytosis; sympathetic nervous system

PMID:
28406285
PMCID:
PMC5541362
DOI:
10.1021/acschemneuro.7b00026
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center