An interplay between the serotonin transporter (SERT) and 5-HT receptors controls stimulus-secretion coupling in sympathoadrenal chromaffin cells
Open accessAbstract
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.
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5-HT can exert an inhibitory effect on epinephrine secretion from adrenal chromaffin cells.
“It is worth noting that 5-HT can exert an inhibitory effect on epinephrine secretion from adrenal chromaffin cells (Brindley et al., 2016).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Brindley et al., 2016
Adrenal chromaffin cells recycle 5-HT through serotonin transporter (SERT).
“It has been shown that adrenal chromaffin cells recycle 5-HT through serotonin transporter (SERT) (Brindley et al., 2016; Linder et al., 2009).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Brindley et al., 2016
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- Authors
- Brindley, R. L., Bauer, M. B., Blakely, R. D., & Currie, K. P. M.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Currie, Kevin P.M.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 110
- Issue
- Pt A
- Pages
- 438-448
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC5028315
- OpenAlex
- W2513237461
- Cited by
- 26
- References
- 62
- Citations by year
- 2025: 4 · 2023: 7 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 3
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R21 NS081429, P50 M096972)
- Department of Anesthesiology at Vanderbilt University Medical Center
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- serotonin transporter, 5-HT1A receptor, adrenal chromaffin cells, catecholamine release, stimulus-secretion coupling, exocytosis, vesicle fusion, SERT knockout mice, WAY-100635, 8-OH-DPAT, escitalopram
- MeSH terms
- Adrenal Glands, Animals, Calcium, Cations, Divalent, Cells, Cultured, Exocytosis, Male, Membrane Potentials, Mice, Inbred C57BL, Receptors, Serotonin, Serotonin, Mice, Knockout, Serotonin Agents, Chromaffin Cells, Calcium Channels, N-Type, Potassium Channels, Voltage-Gated, Serotonin Plasma Membrane Transport Proteins
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