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

Brindley, Rebecca L.; Bauer, Mary Beth; Blakely, Randy D.; Currie, Kevin P. M.

doi:10.1016/j.neuropharm.2016.08.015

Cited by 21 publications

(43 citation statements)

References 60 publications

(81 reference statements)

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“…Consistent with a local signaling role for 5-HT in adrenal chromaffin cells, our recent work revealed that catecholamine secretion can be inhibited by 5-HT 1A receptors 85 . In these studies, we monitored catecholamine release from mouse chromaffin cells ex vivo using carbon fiber amperometry, which enables the detection of quantal vesicular release events.…”

Section: Sert Modulates 5-ht1a Receptor-mediated Inhibition Of Catechsupporting

confidence: 76%

“…These receptors are all thought to act predominantly by inhibition of I Ca 72, 93 . In contrast, 5-HT 1A receptors do not modulate Ca 2+ channels, K + channels, or intracellular Ca 2+ signaling in chromaffin cells 85 . We postulate that the distinct mechanism of 5-HT 1A receptors, coupled with the modulatory influence of SERT, might fine-tune serotonergic signaling to control catecholamine secretion during periods of intense stimulation (i.e.…”

Section: Is Stress-evoked Catecholamine Secretion Fine-tuned By Serotmentioning

confidence: 80%

“…In the CNS, 5-HT 1A receptors inhibit voltage-gated Ca 2+ channel currents ( I Ca ) and somatodendritic 5-HT 1A receptors can also modulate cellular excitability through K + channel activation 94-99 . Surprisingly, although the inhibition of catecholamine secretion by 5-HT 1A receptors in adrenal chromaffin cells involved G i/o -type G proteins and Gβγ signaling, it did not involve modulation of Ca 2+ channels, K + channels, or changes in intracellular [Ca 2+ ] 85 . Previous reports have shown that Gβγ can inhibit secretion independently from Ca 2+ channel regulation in chromaffin cells 100, 101 and neurons 102-104 .…”

Section: Sert Modulates 5-ht1a Receptor-mediated Inhibition Of Catechmentioning

confidence: 86%

“…Moreover, when 5-HT was infused into rodents, the adrenal medulla displayed prominent SERT-mediated accumulation of exogenous 5-HT 82 . Conversely, the 5-HT content of adrenal glands isolated from SERT -/- mice or rats was dramatically reduced (≈ 80%) compared to wild-type controls, with no change in the catecholamine content 16, 82, 85 . A likely source of 5-HT is the circulation; the adrenal gland is highly vascularized and blood contains large amounts of 5-HT, although most of this is sequestered into platelets by SERT-mediated uptake 86, 87 .…”

Section: Multiple Roles For Sert In Sympathoadrenal Chromaffin Cellsmentioning

confidence: 90%

“…For example, the amount of transmitter released by unitary vesicular fusion events (i.e. quantal size) was decreased by ≈35 % in SERT -/- cells compared to wild-type cells, even in the absence of extracellular 5-HT and regardless of 5-HT receptor activation 85 . Further experiments will be required to confirm this finding and identify the underlying mechanism.…”

Section: Sert / 5-ht Might Modulate the Late Steps Of Exocytosismentioning

confidence: 99%

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

Brindley

Bauer

Blakely

et al. 2017

ACS Chem. Neurosci.

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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.

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Section: Sert Modulates 5-ht1a Receptor-mediated Inhibition Of Catechsupporting

confidence: 76%

Section: Is Stress-evoked Catecholamine Secretion Fine-tuned By Serotmentioning

confidence: 80%

Section: Sert Modulates 5-ht1a Receptor-mediated Inhibition Of Catechmentioning

confidence: 86%

Section: Multiple Roles For Sert In Sympathoadrenal Chromaffin Cellsmentioning

confidence: 90%

Section: Sert / 5-ht Might Modulate the Late Steps Of Exocytosismentioning

confidence: 99%

See 3 more Smart Citations

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

Brindley

Bauer

Blakely

et al. 2017

ACS Chem. Neurosci.

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show abstract

Brain Chemistry: Neurotransmitters

Berger¹,

Hashemi²

2018

Reference Module in Chemistry, Molecular Sciences and Chemical Engineering

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Serotonin in Central Cardiovascular Regulation

Pilowsky

2019

Serotonin

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

Cited by 21 publications

References 60 publications

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

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

Brain Chemistry: Neurotransmitters

Serotonin in Central Cardiovascular Regulation

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