Serotonin and Serotonin Transporters in the Adrenal Medulla: A Potential Hub for Modulation of the Sympathetic Stress Response
| Autor: | Randy D. Blakely, Mary Beth Bauer, Kevin P. M. Currie, Rebecca L. Brindley |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Serotonin medicine.medical_specialty Sympathetic nervous system Sympathetic Nervous System Physiology Chromaffin Cells Cognitive Neuroscience Central nervous system Serotonergic Synaptic Transmission Biochemistry Article 03 medical and health sciences 0302 clinical medicine Stress Physiological Internal medicine medicine Animals Humans 5-HT receptor Serotonin transporter Serotonin Plasma Membrane Transport Proteins biology business.industry Cell Biology General Medicine 030104 developmental biology Endocrinology medicine.anatomical_structure Adrenal Medulla biology.protein Catecholamine Arousal business Adrenal medulla Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | ACS Chemical Neuroscience. 8:943-954 |
| ISSN: | 1948-7193 |
| DOI: | 10.1021/acschemneuro.7b00026 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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