@article{8479e8ae5b6b464c90ffd1b29c4d3640,
title = "Adrenal serotonin derives from accumulation by the antidepressant-sensitive serotonin transporter",
abstract = "Adrenal chromaffin cells comprise the neuroendocrine arm of the sympathetic nervous system and secrete catecholamines to coordinate the appropriate stress response. Deletion of the serotonin (5-HT) transporter (SERT) gene in mice (SERT−/− mice) or pharmacological block of SERT function in rodents and humans augments this sympathoadrenal stress response (epinephrine secretion). The prevailing assumption is that loss of CNS SERT alters central drive to the peripheral sympathetic nervous system. Adrenal chromaffin cells also prominently express SERT where it might coordinate accumulation of 5-HT for reuse in the autocrine control of stress-evoked catecholamine secretion. To help test this hypothesis, we have generated a novel mouse model with selective excision of SERT in the peripheral sympathetic nervous system (SERTΔTH), generated by crossing floxed SERT mice with tyrosine hydroxylase Cre driver mice. SERT expression, assessed by western blot, was abolished in the adrenal gland but not perturbed in the CNS of SERTΔTH mice. SERT-mediated [3H] 5-HT uptake was unaltered in midbrain, hindbrain, and spinal cord synaptosomes, confirming transporter function was intact in the CNS. Endogenous midbrain and whole blood 5-HT homeostasis was unperturbed in SERTΔTH mice, contrasting with the depleted 5-HT content in SERT−/− mice. Selective SERT excision reduced adrenal gland 5-HT content by ≈ 50% in SERTΔTH mice but had no effect on adrenal catecholamine content. This novel model confirms that SERT expressed in adrenal chromaffin cells is essential for maintaining wild-type levels of 5-HT and provides a powerful tool to help dissect the role of SERT in the sympathetic stress response.",
author = "Brindley, {Rebecca L.} and Bauer, {Mary Beth} and Walker, {L. Anne} and Quinlan, {Meagan A.} and Carneiro, {Ana M.D.} and Sze, {Ji Ying} and Blakely, {Randy D.} and Currie, {Kevin P.M.}",
note = "Funding Information: We thank Ginger Milne and Benlian Gao of the Vanderbilt Brain Institute Neurochemistry core laboratory in which HPLC analyses were performed. We thank Pat Levitt and Hsiao-Huei Wu for multiplex fluorescent in situ hybridization assays performed in the Molecular Neuroanatomy core of the Vanderbilt Silvio O. Conte Center for Neuroscience and housed at the Saban Research Institute, Children{\textquoteright}s Hospital of Los Angeles. We also acknowledge Chris Svitek for initial help with the mouse colony. This work was supported by the American Heart Association [Grant 17GRNT33661156 ] and the National Institutes of Health [Grant P50 MH096972 ]. Generation of floxed SERT mice was supported by the National Institutes of Health [Grant MH105839 (to JYS)]. The sponsors had no role in the study design, collection/analysis/interpretation of the data, or in the writing of the manuscript for publication. The authors have no conflicts of interest to declare. Funding Information: We thank Ginger Milne and Benlian Gao of the Vanderbilt Brain Institute Neurochemistry core laboratory in which HPLC analyses were performed. We thank Pat Levitt and Hsiao-Huei Wu for multiplex fluorescent in situ hybridization assays performed in the Molecular Neuroanatomy core of the Vanderbilt Silvio O. Conte Center for Neuroscience and housed at the Saban Research Institute, Children's Hospital of Los Angeles. We also acknowledge Chris Svitek for initial help with the mouse colony. This work was supported by the American Heart Association [Grant 17GRNT33661156] and the National Institutes of Health [Grant P50 MH096972]. Generation of floxed SERT mice was supported by the National Institutes of Health [Grant MH105839 (to JYS)]. The sponsors had no role in the study design, collection/analysis/interpretation of the data, or in the writing of the manuscript for publication. The authors have no conflicts of interest to declare. Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",
year = "2019",
month = feb,
doi = "10.1016/j.phrs.2018.06.008",
language = "English (US)",
volume = "140",
pages = "56--66",
journal = "Pharmacological Research",
issn = "1043-6618",
publisher = "Academic Press Inc.",
}